Prolactin: Difference between revisions

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Discovered in non-human animals around 1930 by [[Oscar Riddle]]<ref name="Riddle_1935">
Discovered in non-human animals around 1930 by [[Oscar Riddle]]<ref name="Riddle_1935">
{{cite journal | vauthors = Bates R, Riddle O | title = The preparation of prolactin | journal = Journal of Pharmacolgy and Experimental Therapeutics | volume = 55 | issue = 3 | pages = 365–371 | date = November 1935 | url = http://jpet.aspetjournals.org/content/55/3/365.abstract }}</ref> and confirmed in humans in 1970 by [[Henry Friesen]]<ref name="Friesen_1970">
{{cite journal | vauthors = Bates R, Riddle O | title = The preparation of prolactin | journal = Journal of Pharmacology and Experimental Therapeutics | volume = 55 | issue = 3 | pages = 365–371 | date = November 1935 | url = http://jpet.aspetjournals.org/content/55/3/365.abstract }}</ref> and confirmed in humans in 1970 by [[Henry Friesen]]<ref name="Friesen_1970">
{{cite journal | vauthors = Friesen H, Guyda H, Hardy J | title = The biosynthesis of human growth hormone and prolactin | journal = The Journal of Clinical Endocrinology and Metabolism | volume = 31 | issue = 6 | pages = 611–24 | date = Dec 1970 | pmid = 5483096 | doi = 10.1210/jcem-31-6-611 | url = http://jcem.endojournals.org/content/31/6/611.abstract }}</ref> prolactin is a [[peptide hormone]],  encoded by the ''PRL'' [[gene]].<ref name="pmid2567059">
{{cite journal | vauthors = Friesen H, Guyda H, Hardy J | title = The biosynthesis of human growth hormone and prolactin | journal = The Journal of Clinical Endocrinology and Metabolism | volume = 31 | issue = 6 | pages = 611–24 | date = Dec 1970 | pmid = 5483096 | doi = 10.1210/jcem-31-6-611 | url = http://jcem.endojournals.org/content/31/6/611.abstract }}</ref> prolactin is a [[peptide hormone]],  encoded by the ''PRL'' [[gene]].<ref name="pmid2567059">
{{cite journal | vauthors = Evans AM, Petersen JW, Sekhon GS, DeMars R | title = Mapping of prolactin and tumor necrosis factor-beta genes on human chromosome 6p using lymphoblastoid cell deletion mutants | journal = Somatic Cell and Molecular Genetics | volume = 15 | issue = 3 | pages = 203–13 | date = May 1989 | pmid = 2567059 | doi = 10.1007/BF01534871 }}</ref>
{{cite journal | vauthors = Evans AM, Petersen JW, Sekhon GS, DeMars R | title = Mapping of prolactin and tumor necrosis factor-beta genes on human chromosome 6p using lymphoblastoid cell deletion mutants | journal = Somatic Cell and Molecular Genetics | volume = 15 | issue = 3 | pages = 203–13 | date = May 1989 | pmid = 2567059 | doi = 10.1007/BF01534871 }}</ref>


In mammals, prolactin is associated with milk production; in fish it is thought to be related to control of water and salt balance. Prolactin also acts in a [[cytokine]]-like manner and as an important regulator of the [[immune system]]. It has important cell cycle-related functions as a growth-, differentiating- and anti-[[apoptotic]] factor. As a growth factor, binding to cytokine-like receptors, it influences [[hematopoiesis]], [[angiogenesis]] and is involved in the regulation of blood clotting through several pathways. The hormone acts in [[endocrine]], [[Autocrine signalling|autocrine]] and [[Paracrine signalling|paracrine]] manner through the [[prolactin receptor]] and a large number of [[cytokine receptor]]s.<ref name="Bole-Feysot_1998">{{cite journal | vauthors = Bole-Feysot C, Goffin V, Edery M, Binart N, Kelly PA | title = Prolactin (PRL) and its receptor: actions, signal transduction pathways and phenotypes observed in PRL receptor knockout mice | journal = Endocrine Reviews | volume = 19 | issue = 3 | pages = 225–68 | date = Jun 1998 | pmid = 9626554 | doi = 10.1210/er.19.3.225 }}</ref>
In mammals, prolactin is associated with milk production; in fish it is thought to be related to the control of water and salt balance. Prolactin also acts in a [[cytokine]]-like manner and as an important regulator of the [[immune system]]. It has important cell cycle-related functions as a growth-, differentiating- and anti-[[apoptotic]] factor. As a growth factor, binding to cytokine-like receptors, it influences [[hematopoiesis]], [[angiogenesis]] and is involved in the regulation of blood clotting through several pathways. The hormone acts in [[endocrine]], [[Autocrine signalling|autocrine]] and [[Paracrine signalling|paracrine]] manner through the [[prolactin receptor]] and a large number of [[cytokine receptor]]s.<ref name="Bole-Feysot_1998">{{cite journal | vauthors = Bole-Feysot C, Goffin V, Edery M, Binart N, Kelly PA | title = Prolactin (PRL) and its receptor: actions, signal transduction pathways and phenotypes observed in PRL receptor knockout mice | journal = Endocrine Reviews | volume = 19 | issue = 3 | pages = 225–68 | date = Jun 1998 | pmid = 9626554 | doi = 10.1210/er.19.3.225 }}</ref>


Pituitary prolactin secretion is regulated by endocrine neurons in the [[hypothalamus]]. The most important of these are the neurosecretory [[Tuberoinfundibular pathway|tuberoinfundibulum]] (TIDA) neurons of the [[arcuate nucleus]]<nowiki/> that secrete [[dopamine]] (aka Prolactin Inhibitory Hormone) to act on the [[D2 receptor|D<sub>2</sub> receptor]]s of [[lactotrophs]], causing [[:wikt:inhibition|inhibition]] of prolactin secretion. [[Thyrotropin-releasing factor]] (thyrotropin-releasing hormone) has a [[stimulation|stimulatory]] effect on prolactin release, however prolactin is the only [[Anterior pituitary|adenohypophyseal]] hormone whose principal control is inhibitory.
Pituitary prolactin secretion is regulated by endocrine neurons in the [[hypothalamus]]. The most important of these are the neurosecretory [[Tuberoinfundibular pathway|tuberoinfundibulum]] (TIDA) neurons of the [[arcuate nucleus]]<nowiki/> that secrete [[dopamine]] (aka Prolactin Inhibitory Hormone) to act on the [[D2 receptor|D<sub>2</sub> receptor]]s of [[lactotrophs]], causing [[:wikt:inhibition|inhibition]] of prolactin secretion. [[Thyrotropin-releasing factor]] (thyrotropin-releasing hormone) has a [[stimulation|stimulatory]] effect on prolactin release, however prolactin is the only [[Anterior pituitary|adenohypophyseal]] hormone whose principal control is inhibitory.
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Prolactin also stimulates proliferation of [[oligodendrocyte precursor cell]]s. These cells differentiate into [[oligodendrocyte]]s, the cells responsible for the formation of [[myelin]] coatings on [[axon]]s in the [[central nervous system]].<ref name="pmid17314279">{{cite journal | vauthors = Gregg C, Shikar V, Larsen P, Mak G, Chojnacki A, Yong VW, Weiss S | title = White matter plasticity and enhanced remyelination in the maternal CNS | journal = The Journal of Neuroscience | volume = 27 | issue = 8 | pages = 1812–23 | date = Feb 2007 | pmid = 17314279 | doi = 10.1523/JNEUROSCI.4441-06.2007 }}</ref>
Prolactin also stimulates proliferation of [[oligodendrocyte precursor cell]]s. These cells differentiate into [[oligodendrocyte]]s, the cells responsible for the formation of [[myelin]] coatings on [[axon]]s in the [[central nervous system]].<ref name="pmid17314279">{{cite journal | vauthors = Gregg C, Shikar V, Larsen P, Mak G, Chojnacki A, Yong VW, Weiss S | title = White matter plasticity and enhanced remyelination in the maternal CNS | journal = The Journal of Neuroscience | volume = 27 | issue = 8 | pages = 1812–23 | date = Feb 2007 | pmid = 17314279 | doi = 10.1523/JNEUROSCI.4441-06.2007 }}</ref>


Other actions include contributing to [[pulmonary surfactant]] synthesis of the fetal [[lung]]s at the end of the pregnancy and [[immune tolerance]] of the fetus by the maternal organism during pregnancy. Prolactin delays hair regrowth in mice.<ref name="pmid17088411">{{cite journal | vauthors = Craven AJ, Nixon AJ, Ashby MG, Ormandy CJ, Blazek K, Wilkins RJ, Pearson AJ | title = Prolactin delays hair regrowth in mice | journal = The Journal of Endocrinology | volume = 191 | issue = 2 | pages = 415–25 | date = Nov 2006 | pmid = 17088411 | doi = 10.1677/joe.1.06685 }}</ref> Prolactin promotes [[neurogenesis]] in maternal and [[fetal]] brains.<ref name="pmid12511652">{{cite journal | vauthors = Shingo T, Gregg C, Enwere E, Fujikawa H, Hassam R, Geary C, Cross JC, Weiss S | title = Pregnancy-stimulated neurogenesis in the adult female forebrain mediated by prolactin | journal = Science | volume = 299 | issue = 5603 | pages = 117–20 | date = Jan 2003 | pmid = 12511652 | doi = 10.1126/science.1076647 }}</ref><ref name="pmid21820505">{{cite journal | vauthors = Larsen CM, Grattan DR | title = Prolactin, neurogenesis, and maternal behaviors | journal = Brain, Behavior, and Immunity | volume = 26 | issue = 2 | pages = 201–9 | date = Feb 2012 | pmid = 21820505 | doi = 10.1016/j.bbi.2011.07.233 }}</ref>
Other actions include contributing to [[pulmonary surfactant]] synthesis of the fetal [[lung]]s at the end of the pregnancy and [[immune tolerance]] of the fetus by the maternal organism during pregnancy. Prolactin promotes [[neurogenesis]] in maternal and [[fetal]] brains.<ref name="pmid12511652">{{cite journal | vauthors = Shingo T, Gregg C, Enwere E, Fujikawa H, Hassam R, Geary C, Cross JC, Weiss S | title = Pregnancy-stimulated neurogenesis in the adult female forebrain mediated by prolactin | journal = Science | volume = 299 | issue = 5603 | pages = 117–20 | date = Jan 2003 | pmid = 12511652 | doi = 10.1126/science.1076647 }}</ref><ref name="pmid21820505">{{cite journal | vauthors = Larsen CM, Grattan DR | title = Prolactin, neurogenesis, and maternal behaviors | journal = Brain, Behavior, and Immunity | volume = 26 | issue = 2 | pages = 201–9 | date = Feb 2012 | pmid = 21820505 | doi = 10.1016/j.bbi.2011.07.233 }}</ref>
 
=== Functions in other vertebrate species ===
 
The primary function of prolactin in [[fish]] is [[osmoregulation]]<ref name="pmid16406056">{{cite journal | vauthors = Sakamoto T, McCormick SD | title = Prolactin and growth hormone in fish osmoregulation | journal = General and Comparative Endocrinology | volume = 147 | issue = 1 | pages = 24—30 | date = May 2006 | pmid = 16406056 | doi = 10.1016/j.ygcen.2005.10.008 }}</ref>, i.e., controlling the movement of water and salts between the tissues of the fish and the surrounding water. Like mammals, however, prolactin in fish also has reproductive functions, including promoting sexual maturation and inducing breeding cycles, as well as brooding and parental care.<ref name="pmid23791758">{{cite journal | vauthors = Whittington CM, Wilson AB | title = The role of prolactin in fish reproduction | journal = General and Comparative Endocrinology | volume = 191 | pages = 123—36 | date = September 2013 | pmid = 23791758 | doi = 10.1016/j.ygcen.2013.05.027 }}</ref> In the South American [[Discus (fish)|discus]], prolactin may also regulate the production of a skin secretion that provides food for larval [[Juvenile fish|fry]].<ref name="pmid19272315">{{cite journal | vauthors = Khong HK, Kuah MK, Jaya-Ram A, Shu-Chien AC | title = Prolactin receptor mRNA is upregulated in discus fish (Symphysodon aequifasciata) skin during parental phase | journal = Comparative Biochemistry and Physiology Part B: Biochemistry and Molecular Biology | volume = 153 | issue = 1 | pages = 18—28 | date = May 2009 | pmid = 19272315 | doi = 10.1016/j.cbpb.2009.01.005 }}</ref> An increase in brooding behaviour caused by prolactin has been reported in [[chicken|hens]].<ref name="pmid15971519">{{cite journal | vauthors = Jiang RS, Xu GY, Zhang XQ, Yang N | title = Association of polymorphisms for prolactin and prolactin receptor genes with broody traits in chickens | journal = Poltry Science | volume = 84 | issue = 6 | pages = 839—845 | date = June 2005 | pmid = 15971519 | doi = 10.1093/ps/84.6.839 }}</ref>
 
Prolactin and [[prolactin receptor|its receptor]] are expressed in the skin, specifically in the hair follicles, where they regulate hair growth and moulting in an [[autocrine]] fashion.<ref name="pmid12707045">{{cite journal | vauthors = Foitzik K, Krause K, Nixon AJ, Ford CA, Ohnemus U, Pearson AJ, Paus R | title = Prolactin and Its Receptor Are Expressed in Murine Hair Follicle Epithelium, Show Hair Cycle-Dependent Expression, and Induce Catagen | journal = The American Journal of Pathology | volume = 162 | issue = 5 | pages = 1611–21 | date = May 2003 | pmid = 12707045 | pmc = 1851183 | doi = 10.1016/S0002-9440(10)64295-2 }}</ref><ref name="pmid11356702">{{cite journal | vauthors = Craven AJ, Ormandy CJ, Robertson FG, Wilkins RJ, Kelly PA, Nixon AJ, Pearson AJ | title = Prolactin Signaling Influences the Timing Mechanism of the Hair Follicle: Analysis of Hair Growth Cycles in Prolactin Receptor Knockout Mice | journal = Endocrinology | volume = 142 | issue = 6 | pages = 2533–9 | date = June 2001 | pmid = 11356702 | doi = 10.1210/endo.142.6.8179 }}</ref> Elevated levels of prolactin can inhibit hair growth<ref name="pmid16507890">{{cite journal | vauthors = Foitzik K, Krause K, Conrad F, Nakamura M, Funk W, Paus R | title = Human scalp hair follicles are both a target and a source of prolactin, which serves as an autocrine and/or paracrine promoter of apoptosis-driven hair follicle regression | journal = The American Journal of Pathology | volume = 168 | issue = 3 | pages = 748–56 | date = March 2006 | pmid = 16507890 | pmc = 1606541 | doi = 10.2353/ajpath.2006.050468 }}</ref>, and knock-out [[mutation|mutations]] in the prolactin gene cause increased hair length in cattle<ref name="pmid25519203">{{cite journal | vauthors = Littlejohn MD, Henty KM, Tiplady K, Johnson T, Harland C, Lopdell T, Sherlock RG, Li W, Lukefahr SD, Shanks BC, Garrick DJ, Snell RG, Spelman RJ, Davis SR | title = Functionally reciprocal mutations of the prolactin signalling pathway define hairy and slick cattle | journal = Nature Communications | volume = 5 | pages = 5861 | date = December 2014 | pmid = 25519203 | pmc = 4284646 | doi = 10.1038/ncomms6861 }}</ref> and mice.<ref name="pmid11356702"/> Conversely, mutations in the prolactin receptor can cause reduced hair growth, resulting in the "slick" phenotype in cattle.<ref name="pmid25519203"/><ref name="pmid29527221">{{cite journal | vauthors = Porto-Neto LR, Bickhart DM, Landaeta-Hernandez AJ, Utsunomiya YT, Pagan M, Jimenez E, Hansen PJ, Dikmen S, Schroeder SG, Kim ES, Sun J, Crespo E, Amati N, Cole JB, Null DJ, Garcia JF, Reverter A, Barendse W, Sonstegard TS | title = Convergent Evolution of Slick Coat in Cattle through Truncation Mutations in the Prolactin Receptor | journal = Frontiers in Genetics | volume = 9 | pages = 57 | date = February 2018 | pmid = 29527221 | pmc = 5829098 | doi = 10.3389/fgene.2018.00057 }}</ref> Additionally, prolactin delays hair regrowth in mice.<ref name="pmid17088411">{{cite journal | vauthors = Craven AJ, Nixon AJ, Ashby MG, Ormandy CJ, Blazek K, Wilkins RJ, Pearson AJ | title = Prolactin delays hair regrowth in mice | journal = The Journal of Endocrinology | volume = 191 | issue = 2 | pages = 415–25 | date = Nov 2006 | pmid = 17088411 | doi = 10.1677/joe.1.06685 }}</ref>
 
Analogous to its effects on hair growth and shedding in mammals, prolactin in birds controls the [[moulting]] of feathers,<ref name="pmid16530194">{{cite journal | vauthors = Dawson A | title = Control of molt in birds: association with prolactin and gonadal regression in starlings | journal = General and Comparative Endocrinology | volume = 147 | issue = 3 | pages = 314–22 | date = July 2006 | pmid = 16530194 | doi = 10.1016/j.ygcen.2006.02.001 }}</ref> as well as the age at onset of feathering in both turkeys and chickens.<ref name="pmid29566646">{{cite journal | vauthors = Derks MF, Herrero-Medrano JM, Crooijmans RP, Vereijken A, Long JA, Megens HJ, Groenen MA | title = Early and late feathering in turkey and chicken: same gene but different mutations | journal = Genetics Selection Evolution | volume = 50 | pages = 7 | date = February 2018 | pmid = 29566646 | pmc = 5863816 | doi = 10.1186/s12711-018-0380-3 }}</ref>


== Regulation ==
== Regulation ==


In humans, prolactin is produced at least in the anterior pituitary, [[decidua]], [[myometrium]], breast, [[lymphocytes]], [[leukocytes]] and [[prostate]].<ref name="Ben-Jonathan_1996">{{cite journal | vauthors = Ben-Jonathan N, Mershon JL, Allen DL, Steinmetz RW | title = Extrapituitary prolactin: distribution, regulation, functions, and clinical aspects | journal = Endocrine Reviews | volume = 17 | issue = 6 | pages = 639–69 | date = Dec 1996 | pmid = 8969972 | doi = 10.1210/edrv-17-6-639 }}</ref><ref name="Gerlo_2006">{{cite journal | vauthors = Gerlo S, Davis JR, Mager DL, Kooijman R | title = Prolactin in man: a tale of two promoters | journal = BioEssays | volume = 28 | issue= issue?id=_renonjXq68C&pg=PA66 |type=Hormones |chapter=III. Structure, Synthesis, Secretion, and Target Cells of the Hypothalamic Releasing Hormones: E. Hypothalamic Control of Prolactin Secretion |page=66 |editor-first1=Anthony W. |editor-last1=Norman |editor-first2=Helen L. |editor-last2=Henry |year=2014 |publisher=Academic Press |isbn=9780080919065 | name-list-format = vanc }}</ref> A key regulator of prolactin production is [[estrogen]]s that enhance growth of prolactin-producing cells and stimulate prolactin production directly, as well as suppressing [[dopamine]].
In humans, prolactin is produced at least in the anterior pituitary, [[decidua]], [[myometrium]], breast, [[lymphocytes]], [[leukocytes]] and [[prostate]].<ref name="Ben-Jonathan_1996">{{cite journal | vauthors = Ben-Jonathan N, Mershon JL, Allen DL, Steinmetz RW | title = Extrapituitary prolactin: distribution, regulation, functions, and clinical aspects | journal = Endocrine Reviews | volume = 17 | issue = 6 | pages = 639–69 | date = Dec 1996 | pmid = 8969972 | doi = 10.1210/edrv-17-6-639 }}</ref><ref name="Gerlo_2006">{{cite journal | vauthors = Gerlo S, Davis JR, Mager DL, Kooijman R | title = Prolactin in man: a tale of two promoters | journal = BioEssays | volume = 28 | issue = 10| pages = 1051–5 | date = Oct 2006 | pmid = 16998840 | pmc = 1891148 | doi = 10.1002/bies.20468 }}</ref>
 
Pituitary PRL is controlled by the [[Pit-1]] [[transcription factor]] that binds to the prolactin gene at several sites. Ultimately dopamine, extrapituitary PRL is controlled by a superdistal promoter and apparently unaffected by dopamine.<ref name="Gerlo_2006" /> The [[thyrotropin-releasing hormone]] and the [[vasoactive intestinal peptide]] stimulate the secretion of prolactin in experimental settings, however their physiological influence is unclear. The main stimulus for prolactin secretion is suckling, the effect of which is neuronally mediated.<ref>{{cite book |url=https://books.google.si/books?id=_renonjXq68C&pg=PA66 |title=Hormones |chapter=III. Structure, Synthesis, Secretion, and Target Cells of the Hypothalamic Releasing Hormones: E. Hypothalamic Control of Prolactin Secretion |page=66 |editor-first1=Anthony W. |editor-last1=Norman |editor-first2=Helen L. |editor-last2=Henry |year=2014 |publisher=Academic Press |isbn=9780080919065 | name-list-format = vanc }}</ref> A key regulator of prolactin production is [[estrogen]]s that enhance growth of prolactin-producing cells and stimulate prolactin production directly, as well as suppressing [[dopamine]].


In decidual cells and in lymphocytes the distal promoter and thus prolactin expression is stimulated by [[Cyclic adenosine monophosphate|cAMP]]. Responsivness to cAMP is mediated by an imperfect cAMP–responsive element and two CAAT/enhancer binding proteins (C/EBP).<ref name="Gerlo_2006" /> [[Progesterone]] upregulates prolactin synthesis in the [[endometrium]] and decreases it in [[myometrium]] and breast glandular tissue.<ref name=Zinger_2003>{{cite journal | vauthors = Zinger M, McFarland M, Ben-Jonathan N | title = Prolactin expression and secretion by human breast glandular and adipose tissue explants | journal = The Journal of Clinical Endocrinology and Metabolism | volume = 88 | issue = 2 | pages = 689–96 | date = Feb 2003 | pmid = 12574200 | doi = 10.1210/jc.2002-021255 }}</ref> Breast and other tissues may express the Pit-1 promoter in addition to the distal promoter.
In decidual cells and in lymphocytes the distal promoter and thus prolactin expression is stimulated by [[Cyclic adenosine monophosphate|cAMP]]. Responsivness to cAMP is mediated by an imperfect cAMP–responsive element and two CAAT/enhancer binding proteins (C/EBP).<ref name="Gerlo_2006" /> [[Progesterone]] upregulates prolactin synthesis in the [[endometrium]] and decreases it in [[myometrium]] and breast glandular tissue.<ref name=Zinger_2003>{{cite journal | vauthors = Zinger M, McFarland M, Ben-Jonathan N | title = Prolactin expression and secretion by human breast glandular and adipose tissue explants | journal = The Journal of Clinical Endocrinology and Metabolism | volume = 88 | issue = 2 | pages = 689–96 | date = Feb 2003 | pmid = 12574200 | doi = 10.1210/jc.2002-021255 }}</ref> Breast and other tissues may express the Pit-1 promoter in addition to the distal promoter.
   
   
Extrapituitary production of prolactin is thought to be special to humans and primates and may serve mostly tissue specific [[paracrine]] and [[autocrine]] purposes. It has been hypothesized that in vertebrates such as mice a similar tissue specific effect is achieved by a large family of prolactin-like proteins controlled by at least 26 paralogous PRL genes not present in primates.<ref name="Gerlo_2006" />
Extrapituitary production of prolactin is thought to be special to humans and primates and may serve mostly tissue-specific [[paracrine]] and [[autocrine]] purposes. It has been hypothesized that in vertebrates such as mice a similar tissue-specific effect is achieved by a large family of prolactin-like proteins controlled by at least 26 paralogous PRL genes not present in primates.<ref name="Gerlo_2006" />


[[Vasoactive intestinal peptide]] and [[peptide histidine isoleucine]] help to regulate prolactin secretion in humans, but the functions of these hormones in birds can be quite different.<ref>{{cite journal | vauthors = Kulick RS, Chaiseha Y, Kang SW, Rozenboim I, El Halawani ME | title = The relative importance of vasoactive intestinal peptide and peptide histidine isoleucine as physiological regulators of prolactin in the domestic turkey | journal = General and Comparative Endocrinology | volume = 142 | issue = 3 | pages = 267–73 | date = Jul 2005 | pmid = 15935152 | doi = 10.1016/j.ygcen.2004.12.024 }}</ref>
[[Vasoactive intestinal peptide]] and [[peptide histidine isoleucine]] help to regulate prolactin secretion in humans, but the functions of these hormones in birds can be quite different.<ref>{{cite journal | vauthors = Kulick RS, Chaiseha Y, Kang SW, Rozenboim I, El Halawani ME | title = The relative importance of vasoactive intestinal peptide and peptide histidine isoleucine as physiological regulators of prolactin in the domestic turkey | journal = General and Comparative Endocrinology | volume = 142 | issue = 3 | pages = 267–73 | date = Jul 2005 | pmid = 15935152 | doi = 10.1016/j.ygcen.2004.12.024 }}</ref>
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In usual circumstances, in the absence of [[galactorrhea]], lactation ceases within one or two weeks following the end of [[breastfeeding]].
In usual circumstances, in the absence of [[galactorrhea]], lactation ceases within one or two weeks following the end of [[breastfeeding]].


Levels can rise after exercise, high-protein meals, minor surgical procedures,<ref>{{cite book |vauthors=Melmed S, Jameson JL |chapter=333 Disorders of the Anterior Pituitary and Hypothalamus |veditors=Jameson JN, Kasper DL, Harrison TR, Braunwald E, Fauci AS, Hauser SL, Longo DL |title=Harrison's principles of internal medicine |publisher=McGraw-Hill Medical Publishing Division |location=New York |year=2005 |edition=16th |pages= |isbn=0-07-140235-7 |oclc= |doi= |accessdate= |url=http://highered.mcgraw-hill.com/sites/0071402357/information_center_view0/}}</ref> following [[epileptic seizures]]<ref name="Mellors">{{cite journal | vauthors = Mellers JD | title = The approach to patients with "non-epileptic seizures" | journal = Postgraduate Medical Journal | volume = 81 | issue = 958 | pages = 498–504 | date = Aug 2005 | pmid = 16085740 | pmc = 1743326 | doi = 10.1136/pgmj.2004.029785 }}</ref> or due to physical or emotional [[Stress (psychological)|stress]].<ref name="medlineplus">{{cite news|url=http://www.nlm.nih.gov/medlineplus/ency/article/003718.htm|title=Prolactin|publisher=MedLine plus|accessdate=2014-10-24}}</ref><ref name="sobrinho-2003">{{cite journal | vauthors = Sobrinho LG | title = Prolactin, psychological stress and environment in humans: adaptation and maladaptation | journal = Pituitary | volume = 6 | issue = 1 | pages = 35–9 | year = 2003 | pmid = 14674722 | doi = 10.1023/A:1026229810876 }}</ref> In a study on female volunteers under hypnosis, prolactin surges resulted from the evocation, with rage, of humiliating experiences, but not from the fantasy of nursing.<ref name="sobrinho-2003" />
Levels can rise after exercise, high-protein meals, minor surgical procedures,<ref>{{cite book |vauthors=Melmed S, Jameson JL |chapter=333 Disorders of the Anterior Pituitary and Hypothalamus |veditors=Jameson JN, Kasper DL, Harrison TR, Braunwald E, Fauci AS, Hauser SL, Longo DL |title=Harrison's principles of internal medicine |publisher=McGraw-Hill Medical Publishing Division |location=New York |year=2005 |edition=16th |pages= |isbn=0-07-140235-7 |oclc= |doi= |accessdate= |url=http://highered.mcgraw-hill.com/sites/0071402357/information_center_view0/}}</ref> following [[epileptic seizures]]<ref name="Mellors">{{cite journal | vauthors = Mellers JD | title = The approach to patients with "non-epileptic seizures" | journal = Postgraduate Medical Journal | volume = 81 | issue = 958 | pages = 498–504 | date = Aug 2005 | pmid = 16085740 | pmc = 1743326 | doi = 10.1136/pgmj.2004.029785 }}</ref> or due to physical or emotional [[Stress (psychological)|stress]].<ref name="medlineplus">{{cite news|url=https://www.nlm.nih.gov/medlineplus/ency/article/003718.htm|title=Prolactin|publisher=MedLine plus|accessdate=2014-10-24}}</ref><ref name="sobrinho-2003">{{cite journal | vauthors = Sobrinho LG | title = Prolactin, psychological stress and environment in humans: adaptation and maladaptation | journal = Pituitary | volume = 6 | issue = 1 | pages = 35–9 | year = 2003 | pmid = 14674722 | doi = 10.1023/A:1026229810876 }}</ref> In a study on female volunteers under hypnosis, prolactin surges resulted from the evocation, with rage, of humiliating experiences, but not from the fantasy of nursing.<ref name="sobrinho-2003" />


Prolactin levels have also been found to rise with use of the drug [[MDMA]].<ref>{{cite journal|title=Ecstasy (MDMA) mimics the post-orgasmic state: impairment of sexual drive and function during acute MDMA-effects may be due to increased prolactin secretion.| pmid=15780482 | doi=10.1016/j.mehy.2004.11.044 | volume=64| issue=5| journal=Med Hypotheses| pages=899–903| vauthors=Passie T, Hartmann U, Schneider U, Emrich HM, Krüger TH}}</ref>
Prolactin levels have also been found to rise with use of the drug [[MDMA]].<ref>{{cite journal|title=Ecstasy (MDMA) mimics the post-orgasmic state: impairment of sexual drive and function during acute MDMA-effects may be due to increased prolactin secretion.| pmid=15780482 | doi=10.1016/j.mehy.2004.11.044 | volume=64| issue=5| journal=Med Hypotheses| pages=899–903| vauthors=Passie T, Hartmann U, Schneider U, Emrich HM, Krüger TH| year=2005}}</ref>


Hypersecretion is more common than hyposecretion. Hyperprolactinemia is the most frequent abnormality of the anterior pituitary tumors, termed [[prolactinoma]]s. Prolactinomas may disrupt the [[hypothalamic-pituitary-gonadal axis]] as prolactin tends to suppress the secretion of GnRH from the hypothalamus and in turn decreases the secretion of [[follicle-stimulating hormone]] (FSH) and [[luteinizing hormone]] (LH) from the anterior pituitary, therefore disrupting the [[Menstrual cycle|ovulatory cycle]].<ref>{{cite web|title=Etiology, diagnosis, and treatment of secondary amenorrhea|url=http://www.uptodate.com/contents/etiology-diagnosis-and-treatment-of-secondary-amenorrhea?detectedLanguage=en&source=search_result&search=etiology+of+secondary+amenorrhea&selectedTitle=1%7E30&provider=noProvider|accessdate=7 November 2013}}</ref> Such hormonal changes may manifest as [[amenorrhea]] and infertility in females as well as impotence in males. Inappropriate lactation ([[Galactorrhea|galactorrhoea]]) is another important clinical sign of prolactinomas.
Hypersecretion is more common than hyposecretion. Hyperprolactinemia is the most frequent abnormality of the anterior pituitary tumors, termed [[prolactinoma]]s. Prolactinomas may disrupt the [[hypothalamic-pituitary-gonadal axis]] as prolactin tends to suppress the secretion of [[GnRH]] from the hypothalamus and in turn decreases the secretion of [[follicle-stimulating hormone]] (FSH) and [[luteinizing hormone]] (LH) from the anterior pituitary, therefore disrupting the [[Menstrual cycle|ovulatory cycle]].<ref>{{cite web|title=Etiology, diagnosis, and treatment of secondary amenorrhea|url=http://www.uptodate.com/contents/etiology-diagnosis-and-treatment-of-secondary-amenorrhea?detectedLanguage=en&source=search_result&search=etiology+of+secondary+amenorrhea&selectedTitle=1%7E30&provider=noProvider|accessdate=7 November 2013}}</ref> Such hormonal changes may manifest as [[amenorrhea]] and infertility in females as well as impotence in males. Inappropriate lactation ([[Galactorrhea|galactorrhoea]]) is another important clinical sign of prolactinomas.


== Structure and isoforms ==
== Structure and isoforms ==


The structure of prolactin is similar to that of [[growth hormone]] and [[placental lactogen]]. The molecule is folded due to the activity of three [[disulfide bond]]s. Significant heterogeneity of the molecule has been described, thus [[bioassay]]s and [[immunoassay]]s can give different results due to differing [[glycosylation]], [[phosphorylation]][[sulfation|sandulfation]], as well as degradation. The non-glycosylated form of prolactin is the dominant form at is secreted by the [[pituitary gland]].
The structure of prolactin is similar to that of [[growth hormone]] and [[placental lactogen]]. The molecule is folded due to the activity of three [[disulfide bond]]s. Significant heterogeneity of the molecule has been described, thus [[bioassay]]s and [[immunoassay]]s can give different results due to differing [[glycosylation]], [[phosphorylation]] and [[sulfation]], as well as degradation. The non-glycosylated form of prolactin is the dominant form that is secreted by the [[pituitary gland]].


The three different sizes of prolactin are:
The three different sizes of prolactin are:
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== Prolactin receptor ==
== Prolactin receptor ==
{{Main article|Prolactin receptor}}
{{Main|Prolactin receptor}}


Prolactin receptors are present in the [[Mammillary body|mammillary glands]], [[Ovary|ovaries]], pituitary glands, heart, lung, [[thymus]], [[spleen]], liver, pancreas, [[kidney]], [[adrenal gland]], [[uterus]], [[skeletal muscle]], skin and areas of the [[central nervous system]].<ref name=Mancini2008>{{cite journal | vauthors = Mancini T, Casanueva FF, Giustina A | title = Hyperprolactinemia and prolactinomas | journal = Endocrinology and Metabolism Clinics of North America | volume = 37 | issue = 1 | pages = 67–99, viii | date = Mar 2008 | pmid = 18226731 | doi = 10.1016/j.ecl.2007.10.013 }}</ref> When prolactin binds to the receptor, it causes it to [[Dimer (chemistry)|dimerize]] with another prolactin receptor. This results in the activation of [[Janus kinase 2]], a [[tyrosine kinase]] that initiates the [[JAK-STAT pathway]]. Activation also results in the activation of [[mitogen-activated protein kinases]] and [[Src kinase]].<ref name=Mancini2008/>
Prolactin receptors are present in the [[Mammillary body|mammillary glands]], [[Ovary|ovaries]], pituitary glands, heart, lung, [[thymus]], [[spleen]], liver, pancreas, [[kidney]], [[adrenal gland]], [[uterus]], [[skeletal muscle]], skin and areas of the [[central nervous system]].<ref name=Mancini2008>{{cite journal | vauthors = Mancini T, Casanueva FF, Giustina A | title = Hyperprolactinemia and prolactinomas | journal = Endocrinology and Metabolism Clinics of North America | volume = 37 | issue = 1 | pages = 67–99, viii | date = Mar 2008 | pmid = 18226731 | doi = 10.1016/j.ecl.2007.10.013 }}</ref> When prolactin binds to the receptor, it causes it to [[Dimer (chemistry)|dimerize]] with another prolactin receptor. This results in the activation of [[Janus kinase 2]], a [[tyrosine kinase]] that initiates the [[JAK-STAT pathway]]. Activation also results in the activation of [[mitogen-activated protein kinases]] and [[Src kinase]].<ref name=Mancini2008/>
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== Diagnostic use ==
== Diagnostic use ==
Prolactin levels may be checked as part of a [[sex hormone]] workup, as elevated prolactin secretion can suppress the secretion of FSH and GnRH, leading to [[hypogonadism]] and sometimes causing [[erectile dysfunction]].
Prolactin levels may be checked as part of a [[sex hormone]] workup, as elevated prolactin secretion can suppress the secretion of FSH and [[GnRH]], leading to [[hypogonadism]] and sometimes causing [[erectile dysfunction]].


Prolactin levels may be of some use in distinguishing [[seizure|epileptic seizures]] from [[psychogenic non-epileptic seizures]]. The serum prolactin level usually rises following an epileptic seizure.<ref>{{cite journal | vauthors = Banerjee S, Paul P, Talib VJ | title = Serum prolactin in seizure disorders | journal = Indian Pediatrics | volume = 41 | issue = 8 | pages = 827–31 | date = Aug 2004 | pmid = 15347871 }}</ref>
Prolactin levels may be of some use in distinguishing [[seizure|epileptic seizures]] from [[psychogenic non-epileptic seizures]]. The serum prolactin level usually rises following an epileptic seizure.<ref>{{cite journal | vauthors = Banerjee S, Paul P, Talib VJ | title = Serum prolactin in seizure disorders | journal = Indian Pediatrics | volume = 41 | issue = 8 | pages = 827–31 | date = Aug 2004 | pmid = 15347871 }}</ref>
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== Units and unit conversions ==
== Units and unit conversions ==


The serum concentration of prolactin can be given in [[mass concentration (chemistry)|mass concentration]] ([[microgram|µg]]/[[litre|L]] or [[nanogram|ng]]/[[millilitre|mL]]), [[molar concentration]] ([[nanomole|nmol]]/L or [[picomole|pmol]]/L) or in [[international unit]]s (typically mIU/L). The current IU is calibrated against the third International Standard for Prolactin, IS 84/500.<ref name="Schulster 1989">{{cite journal | vauthors = Schulster D, Gaines Das RE, Jeffcoate SL | title = International Standards for human prolactin: calibration by international collaborative study | journal = The Journal of Endocrinology | volume = 121 | issue = 1 | pages = 157–66 | date = Apr 1989 | pmid = 2715755 | doi = 10.1677/joe.0.1210157 }}</ref><ref name="urlwhqlibdoc.who.int">{{cite web | url = http://whqlibdoc.who.int/trs/WHO_TRS_786.pdf | title = WHO Expert Committee on Biological Standardization | year = 1989 | format = | work = Thirty-ninth Report, WHO Technical Report Series | publisher = World Health Organization | pages = | archiveurl = | archivedate = | quote = 86.1520, WHO/BS documents: 86.1520 Add 1, 88.1596 | accessdate = 2009-06-03}}</ref> Reference ampoules of IS 84/500 contain 2.5&nbsp;µg of [[lyophilize]]d human prolactin<ref name="NIBSC instructions">{{cite web | url = http://www.nibsc.ac.uk/documents/ifu/84-500.pdf | title = WHO International Standard, Prolactin, Human. NIBSC code: 84/500, Instructions for use | year = 1989 | format = | work = WHO International Standard, Prolactin, Human. NIBSC code: 84/500, Instructions for use | publisher = NIBSC / Health Protection Agency | pages = | archiveurl = | archivedate = | accessdate = 2011-03-21}}</ref> and have been assigned an activity of .053 International Units.<ref name="Schulster 1989" /><ref name="urlwhqlibdoc.who.int" /> Measurements that are calibrated against the current international standard can be converted into mass units using this ratio of grams to IUs;<ref name="CSCC 1992">{{cite journal | author = Canadian Society of Clinical Chemists | title = Canadian Society of Clinical Chemists position paper: standardization of selected polypeptide hormone measurements | journal = Clinical Biochemistry | volume = 25 | issue = 6 | pages = 415–24 | date = Dec 1992 | pmid = 1477965 | doi = 10.1016/0009-9120(92)90030-V }}</ref> prolactin concentrations expressed in mIU/L can be converted to µg/L by dividing by 21.2. Previous standards use other ratios.<ref name="Gaines Das 1979">{{cite journal | vauthors = Gaines Das RE, Cotes PM | title = International Reference Preparation of human prolactin for immunoassay: definition of the International Unit, report of a collaborative study and comparison of estimates of human prolactin made in various laboratories | journal = The Journal of Endocrinology | volume = 80 | issue = 1 | pages = 157–68 | date = Jan 1979 | pmid = 429949 | doi = 10.1677/joe.0.0800157 }}</ref><ref name="second IRP">{{cite web | url = http://whqlibdoc.who.int/trs/WHO_TRS_725.pdf | title = WHO Expert Committee on Biological Standardization | year = 1985 | format = | work = Thirty-fifth Report, WHO Technical Report Series | publisher = World Health Organization | pages = | archiveurl = | archivedate = | accessdate = 2011-03-21}}</ref><ref name="second IS">{{cite web | url = http://whqlibdoc.who.int/trs/WHO_TRS_760.pdf | title = WHO Expert Committee on Biological Standardization | year = 1987 | format = | work = Thirty-seventh Report, WHO Technical Report Series | publisher = World Health Organization | pages = | archiveurl = | archivedate = | accessdate = 2011-03-21}}</ref><ref name=who1963>{{cite journal | vauthors = Bangham DR, Mussett MV, Stack-Dunne MP | title = THE SECOND INTERNATIONAL STANDARD FOR PROLACTIN | journal = Bulletin of the World Health Organization | volume = 29 | issue = 6 | pages = 721–8 | year = 1963 | pmid = 14107744 | pmc = 2555104 }}</ref>
The serum concentration of prolactin can be given in [[mass concentration (chemistry)|mass concentration]] ([[microgram|µg]]/[[litre|L]] or [[nanogram|ng]]/[[millilitre|mL]]), [[molar concentration]] ([[nanomole|nmol]]/L or [[picomole|pmol]]/L) or in [[international unit]]s (typically mIU/L). The current IU is calibrated against the third International Standard for Prolactin, IS 84/500.<ref name="Schulster 1989">{{cite journal | vauthors = Schulster D, Gaines Das RE, Jeffcoate SL | title = International Standards for human prolactin: calibration by international collaborative study | journal = The Journal of Endocrinology | volume = 121 | issue = 1 | pages = 157–66 | date = Apr 1989 | pmid = 2715755 | doi = 10.1677/joe.0.1210157 }}</ref><ref name="urlwhqlibdoc.who.int">{{cite web | url = http://whqlibdoc.who.int/trs/WHO_TRS_786.pdf | title = WHO Expert Committee on Biological Standardization | year = 1989 | format = | work = Thirty-ninth Report, WHO Technical Report Series | publisher = World Health Organization | pages = | quote = 86.1520, WHO/BS documents: 86.1520 Add 1, 88.1596 | accessdate = 2009-06-03}}</ref> Reference ampoules of IS 84/500 contain 2.5&nbsp;µg of [[lyophilize]]d human prolactin<ref name="NIBSC instructions">{{cite web | url = http://www.nibsc.ac.uk/documents/ifu/84-500.pdf | title = WHO International Standard, Prolactin, Human. NIBSC code: 84/500, Instructions for use | year = 1989 | format = | work = WHO International Standard, Prolactin, Human. NIBSC code: 84/500, Instructions for use | publisher = NIBSC / Health Protection Agency | pages = | archiveurl =https://web.archive.org/web/20111003214114/http://www.nibsc.ac.uk/documents/ifu/84-500.pdf| archivedate =2011-10-03| dead-url = yes | accessdate = 2011-03-21}}</ref> and have been assigned an activity of .053 International Units.<ref name="Schulster 1989" /><ref name="urlwhqlibdoc.who.int" /> Measurements that are calibrated against the current international standard can be converted into mass units using this ratio of grams to IUs;<ref name="CSCC 1992">{{cite journal | author = Canadian Society of Clinical Chemists | title = Canadian Society of Clinical Chemists position paper: standardization of selected polypeptide hormone measurements | journal = Clinical Biochemistry | volume = 25 | issue = 6 | pages = 415–24 | date = Dec 1992 | pmid = 1477965 | doi = 10.1016/0009-9120(92)90030-V }}</ref> prolactin concentrations expressed in mIU/L can be converted to µg/L by dividing by 21.2. Previous standards use other ratios.<ref name="Gaines Das 1979">{{cite journal | vauthors = Gaines Das RE, Cotes PM | title = International Reference Preparation of human prolactin for immunoassay: definition of the International Unit, report of a collaborative study and comparison of estimates of human prolactin made in various laboratories | journal = The Journal of Endocrinology | volume = 80 | issue = 1 | pages = 157–68 | date = Jan 1979 | pmid = 429949 | doi = 10.1677/joe.0.0800157 }}</ref><ref name="second IRP">{{cite web | url = http://whqlibdoc.who.int/trs/WHO_TRS_725.pdf | title = WHO Expert Committee on Biological Standardization | year = 1985 | format = | work = Thirty-fifth Report, WHO Technical Report Series | publisher = World Health Organization | pages = | accessdate = 2011-03-21}}</ref><ref name="second IS">{{cite web | url = http://whqlibdoc.who.int/trs/WHO_TRS_760.pdf | title = WHO Expert Committee on Biological Standardization | year = 1987 | format = | work = Thirty-seventh Report, WHO Technical Report Series | publisher = World Health Organization | pages = | accessdate = 2011-03-21}}</ref><ref name=who1963>{{cite journal | vauthors = Bangham DR, Mussett MV, Stack-Dunne MP | title = THE SECOND INTERNATIONAL STANDARD FOR PROLACTIN | journal = Bulletin of the World Health Organization | volume = 29 | issue = 6 | pages = 721–8 | year = 1963 | pmid = 14107744 | pmc = 2555104 }}</ref>


The first [[International unit#Equality and equivalency of IU for different substances|International Reference Preparation]] (or IRP) of human Prolactin for Immunoassay was established in 1978 (75/504 1st IRP for human Prolactin) at a time when purified human prolactin was in short supply.<ref name="CSCC 1992" /><ref name="Gaines Das 1979" /> Previous standards relied on prolactin from animal sources.<ref name=who1963 /> Purified human prolactin was scarce, heterogeneous, unstable and difficult to characterize. A preparation labelled 81/541 was distributed by the [[World Health Organization|WHO]] [[WHO Expert Committee on Biological Standardization|Expert Committee on Biological Standardization]] without official status and given the assigned value of 50 mIU/ampoule based on an earlier collaborative study.<ref name="CSCC 1992" /><ref name="second IRP" /> It was determined that this preparation behaved anomalously in certain [[immunoassays]] and was not suitable as an IS.<ref name="CSCC 1992" />
The first [[International unit#Equality and equivalency of IU for different substances|International Reference Preparation]] (or IRP) of human Prolactin for Immunoassay was established in 1978 (75/504 1st IRP for human Prolactin) at a time when purified human prolactin was in short supply.<ref name="CSCC 1992" /><ref name="Gaines Das 1979" /> Previous standards relied on prolactin from animal sources.<ref name=who1963 /> Purified human prolactin was scarce, heterogeneous, unstable and difficult to characterize. A preparation labelled 81/541 was distributed by the [[World Health Organization|WHO]] [[WHO Expert Committee on Biological Standardization|Expert Committee on Biological Standardization]] without official status and given the assigned value of 50 mIU/ampoule based on an earlier collaborative study.<ref name="CSCC 1992" /><ref name="second IRP" /> It was determined that this preparation behaved anomalously in certain [[immunoassays]] and was not suitable as an IS.<ref name="CSCC 1992" />
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== Reference ranges ==
== Reference ranges ==


General guidelines for diagnosing prolactin excess ([[hyperprolactinemia]]) define the upper threshold of normal prolactin at 25&nbsp;µg/L for women and 20&nbsp;µg/L for men.<ref name="Mancini2008" /> Similarly, guidelines for diagnosing prolactin deficiency ([[hypoprolactinemia]]) are defined as prolactin levels below 3&nbsp;µg/L in women<ref name="Kauppila 1988">{{cite journal | vauthors = Kauppila A, Martikainen H, Puistola U, Reinilä M, Rönnberg L | title = Hypoprolactinemia and ovarian function | journal = Fertility and Sterility | volume = 49 | issue = 3 | pages = 437–41 | date = Mar 1988 | pmid = 3342895 | doi=10.1016/s0015-0282(16)59769-6}}</ref><ref name="Schwarzler 1997">{{cite journal | vauthors = Schwärzler P, Untergasser G, Hermann M, Dirnhofer S, Abendstein B, Berger P | title = Prolactin gene expression and prolactin protein in premenopausal and postmenopausal human ovaries | journal = Fertility and Sterility | volume = 68 | issue = 4 | pages = 696–701 | date = Oct 1997 | pmid = 9341613 | doi = 10.1016/S0015-0282(97)00320-8 }}</ref> and 5&nbsp;µg/L in men.<ref name="Corona 2009">{{cite journal | vauthors = Corona G, Mannucci E, Jannini EA, Lotti F, Ricca V, Monami M, Boddi V, Bandini E, Balercia G, Forti G, Maggi M | title = Hypoprolactinemia: a new clinical syndrome in patients with sexual dysfunction | journal = The Journal of Sexual Medicine | volume = 6 | issue = 5 | pages = 1457–66 | date = May 2009 | pmid = 19210705 | doi = 10.1111/j.1743-6109.2008.01206.x }}</ref><ref name="Gonzales 1989">{{cite journal | vauthors = Gonzales GF, Velasquez G, Garcia-Hjarles M | title = Hypoprolactinemia as related to seminal quality and serum testosterone | journal = Archives of Andrology | volume = 23 | issue = 3 | pages = 259–65 | year = 1989 | pmid = 2619414 | doi = 10.3109/01485018908986849 }}</ref><ref name="Ufearo 1995">{{cite journal | vauthors = Ufearo CS, Orisakwe OE | title = Restoration of normal sperm characteristics in hypoprolactinemic infertile men treated with metoclopramide and exogenous human prolactin | journal = Clinical Pharmacology and Therapeutics | volume = 58 | issue = 3 | pages = 354–9 | date = Sep 1995 | pmid = 7554710 | doi = 10.1016/0009-9236(95)90253-8 }}</ref> However, different assays and methods for measuring prolactin are employed by different laboratories and as such the [[Reference ranges for blood tests|serum reference range]] for prolactin is often determined by the laboratory performing the measurement.<ref name="Mancini2008" /><ref name="Beltran_2008"/> Furthermore, prolactin levels also vary factors including age,<ref name=immulite/> sex,<ref name=immulite/> [[menstrual cycle]] stage<ref name=immulite/> and pregnancy.<ref name=immulite>[http://www.medical.siemens.com/siemens/en_GLOBAL/gg_diag_FBAs/files/referenzwerte_pdf/IMMULITE_Systeme/prolaktin.pdf Prolaktin] at medical.siemens.com—reference ranges as determined from the IMMULITE assay method</ref> The circumstances surrounding a given prolactin measurement (assay, patient condition, etc.) must therefore be considered before the measurement can be accurately interpreted.<ref name="Mancini2008" />
General guidelines for diagnosing prolactin excess ([[hyperprolactinemia]]) define the upper threshold of normal prolactin at 25&nbsp;µg/L for women and 20&nbsp;µg/L for men.<ref name="Mancini2008" /> Similarly, guidelines for diagnosing prolactin deficiency ([[hypoprolactinemia]]) are defined as prolactin levels below 3&nbsp;µg/L in women<ref name="Kauppila 1988">{{cite journal | vauthors = Kauppila A, Martikainen H, Puistola U, Reinilä M, Rönnberg L | title = Hypoprolactinemia and ovarian function | journal = Fertility and Sterility | volume = 49 | issue = 3 | pages = 437–41 | date = Mar 1988 | pmid = 3342895 | doi=10.1016/s0015-0282(16)59769-6}}</ref><ref name="Schwarzler 1997">{{cite journal | vauthors = Schwärzler P, Untergasser G, Hermann M, Dirnhofer S, Abendstein B, Berger P | title = Prolactin gene expression and prolactin protein in premenopausal and postmenopausal human ovaries | journal = Fertility and Sterility | volume = 68 | issue = 4 | pages = 696–701 | date = Oct 1997 | pmid = 9341613 | doi = 10.1016/S0015-0282(97)00320-8 }}</ref> and 5&nbsp;µg/L in men.<ref name="Corona 2009">{{cite journal | vauthors = Corona G, Mannucci E, Jannini EA, Lotti F, Ricca V, Monami M, Boddi V, Bandini E, Balercia G, Forti G, Maggi M | title = Hypoprolactinemia: a new clinical syndrome in patients with sexual dysfunction | journal = The Journal of Sexual Medicine | volume = 6 | issue = 5 | pages = 1457–66 | date = May 2009 | pmid = 19210705 | doi = 10.1111/j.1743-6109.2008.01206.x }}</ref><ref name="Gonzales 1989">{{cite journal | vauthors = Gonzales GF, Velasquez G, Garcia-Hjarles M | title = Hypoprolactinemia as related to seminal quality and serum testosterone | journal = Archives of Andrology | volume = 23 | issue = 3 | pages = 259–65 | year = 1989 | pmid = 2619414 | doi = 10.3109/01485018908986849 }}</ref><ref name="Ufearo 1995">{{cite journal | vauthors = Ufearo CS, Orisakwe OE | title = Restoration of normal sperm characteristics in hypoprolactinemic infertile men treated with metoclopramide and exogenous human prolactin | journal = Clinical Pharmacology and Therapeutics | volume = 58 | issue = 3 | pages = 354–9 | date = Sep 1995 | pmid = 7554710 | doi = 10.1016/0009-9236(95)90253-8 }}</ref> However, different assays and methods for measuring prolactin are employed by different laboratories and as such the [[Reference ranges for blood tests|serum reference range]] for prolactin is often determined by the laboratory performing the measurement.<ref name="Mancini2008" /><ref name="Beltran_2008"/> Furthermore, prolactin levels also vary factors including age,<ref name=immulite/> sex,<ref name=immulite/> [[menstrual cycle]] stage<ref name=immulite/> and pregnancy.<ref name=immulite>[http://www.medical.siemens.com/siemens/en_GLOBAL/gg_diag_FBAs/files/referenzwerte_pdf/IMMULITE_Systeme/prolaktin.pdf Prolaktin] {{webarchive|url=https://web.archive.org/web/20110728085232/http://www.medical.siemens.com/siemens/en_GLOBAL/gg_diag_FBAs/files/referenzwerte_pdf/IMMULITE_Systeme/prolaktin.pdf |date=28 July 2011 }} at medical.siemens.com—reference ranges as determined from the IMMULITE assay method</ref> The circumstances surrounding a given prolactin measurement (assay, patient condition, etc.) must therefore be considered before the measurement can be accurately interpreted.<ref name="Mancini2008" />


The following chart illustrates the variations seen in normal prolactin measurements across different populations. Prolactin values were obtained from specific control groups of varying sizes using the IMMULITE [[assay]].<ref name=immulite />
The following chart illustrates the variations seen in normal prolactin measurements across different populations. Prolactin values were obtained from specific control groups of varying sizes using the IMMULITE [[assay]].<ref name=immulite />
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=== Decreased levels ===
=== Decreased levels ===
{{Main article|Hypoprolactinemia}}
{{Main|Hypoprolactinemia}}
[[Hypoprolactinemia]], or serum prolactin deficiency, is associated with ovarian dysfunction in women,<ref name="Kauppila 1988" /><ref name="Schwarzler 1997" /> and [[Arteriogenesis|arteriogenic]] [[erectile dysfunction]], [[premature ejaculation]],<ref name="Corona 2009" /> [[oligozoospermia]], [[asthenospermia]], hypofunction of [[seminal vesicles]] and [[hypoandrogenism]]<ref name="Gonzales 1989" /> in men. In one study, normal sperm characteristics were restored when prolactin levels were raised to normal values in hypoprolactinemic men.<ref name="Ufearo 1995" />
[[Hypoprolactinemia]], or serum prolactin deficiency, is associated with ovarian dysfunction in women,<ref name="Kauppila 1988" /><ref name="Schwarzler 1997" /> and [[Arteriogenesis|arteriogenic]] [[erectile dysfunction]], [[premature ejaculation]],<ref name="Corona 2009" /> [[oligozoospermia]], [[asthenospermia]], hypofunction of [[seminal vesicles]] and [[hypoandrogenism]]<ref name="Gonzales 1989" /> in men. In one study, normal sperm characteristics were restored when prolactin levels were raised to normal values in hypoprolactinemic men.<ref name="Ufearo 1995" />


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==In medicine==
==In medicine==
Prolactin is available commercially for use in animals, but not in humans.<ref name="CouttsSmail2014">{{cite book|author1=R. T. Coutts|author2=G. A. Smail|title=Polysaccharides Peptides and Proteins: Pharmaceutical Monographs|url=https://books.google.com/books?id=ojGRBQAAQBAJ&pg=PA153|date=12 May 2014|publisher=Elsevier|isbn=978-1-4831-9612-1|pages=153–}}</ref> It is used to stimulate lactation in animals.<ref name="CouttsSmail2014" /> The [[biological half-life]] of prolactin in humans is around 15–20 minutes.<ref name="Horrobin2012">{{cite book|author=D.F. Horrobin|title=Prolactin: Physiology and Clinical Significance|url=https://books.google.com/books?id=h_Q-BAAAQBAJ&pg=PA13|date=6 December 2012|publisher=Springer Science & Business Media|isbn=978-94-010-9695-9|pages=13–}}</ref> The D<sub>2</sub> receptor is involved in the regulation of prolactin secretion, and agonists of the receptor such as [[bromocriptine]] and [[cabergoline]] decrease prolactin levels while antagonists of the receptor such as [[domperidone]], [[metoclopramide]], [[haloperidol]], [[risperidone]], and [[sulpiride]] increase prolactin levels.<ref name="Johnson2012">{{cite book|author=Martin H. Johnson|title=Essential Reproduction|url=https://books.google.com/books?id=qXpBst5hJs0C&pg=PT40|date=14 December 2012|publisher=John Wiley & Sons|isbn=978-1-118-42388-2|pages=40–}}</ref> D<sub>2</sub> receptor antagonists like domperidone, metoclopramide, and sulpiride are used as [[galactogogue]]s to increase prolatin secretion and induce lactation in humans.<ref name="Riordan2005">{{cite book|author=Jan Riordan|title=Breastfeeding and Human Lactation|url=https://books.google.com/books?id=aiVesab_2bwC&pg=PA468|date=January 2005|publisher=Jones & Bartlett Learning|isbn=978-0-7637-4585-1|pages=468–}}</ref>
Prolactin is available commercially for use in animals, but not in humans.<ref name="CouttsSmail2014">{{cite book| vauthors = Coutts RT, Smail GA | title = Polysaccharides Peptides and Proteins: Pharmaceutical Monographs|url=https://books.google.com/books?id=ojGRBQAAQBAJ&pg=PA153|date=12 May 2014|publisher=Elsevier|isbn=978-1-4831-9612-1|pages=153–}}</ref> It is used to stimulate lactation in animals.<ref name="CouttsSmail2014" /> The [[biological half-life]] of prolactin in humans is around 15–20 minutes.<ref name="Horrobin2012">{{cite book|author=D.F. Horrobin|title=Prolactin: Physiology and Clinical Significance|url=https://books.google.com/books?id=h_Q-BAAAQBAJ&pg=PA13|date=6 December 2012|publisher=Springer Science & Business Media|isbn=978-94-010-9695-9|pages=13–}}</ref> The D<sub>2</sub> receptor is involved in the regulation of prolactin secretion, and agonists of the receptor such as [[bromocriptine]] and [[cabergoline]] decrease prolactin levels while antagonists of the receptor such as [[domperidone]], [[metoclopramide]], [[haloperidol]], [[risperidone]], and [[sulpiride]] increase prolactin levels.<ref name="Johnson2012">{{cite book|author=Martin H. Johnson|title=Essential Reproduction|url=https://books.google.com/books?id=qXpBst5hJs0C&pg=PT40|date=14 December 2012|publisher=John Wiley & Sons|isbn=978-1-118-42388-2|pages=40–}}</ref> D<sub>2</sub> receptor antagonists like domperidone, metoclopramide, and sulpiride are used as [[galactogogue]]s to increase prolatin secretion in pituitary gland and induce lactation in humans.<ref name="Riordan2005">{{cite book|author=Jan Riordan|title=Breastfeeding and Human Lactation|url=https://books.google.com/books?id=aiVesab_2bwC&pg=PA468|date=January 2005|publisher=Jones & Bartlett Learning|isbn=978-0-7637-4585-1|pages=468–}}</ref>


==See also==
==See also==
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==External links==
==External links==
* [http://arbl.cvmbs.colostate.edu/hbooks/pathphys/endocrine/hypopit/prolactin.html Pathophysiology of Endocrine System—Prolactin at colostate.edu]
* {{MedlinePlusEncyclopedia|003718|Prolactin}}
* {{MedlinePlusEncyclopedia|003718|Prolactin}}
* [http://labtestsonline.org/understanding/analytes/prolactin/tab/test Prolactin] - Lab Tests Online
* {{eMedicine|med|1098}}—"Hyperprolactinemia"
* {{eMedicine|med|1914}}—"Prolactin Deficiency"
* [http://www.endo-society.org/guidelines/final/upload/Diagnosis-Treatment-of-Hyperprolactinemia.pdf] - "Endocrine Society Guidelines"


{{Hormones}}
{{Hormones}}

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Prolactin (PRL), also known as luteotropic hormone or luteotropin, is a protein that is best known for its role in enabling mammals, usually females, to produce milk. It is influential in over 300 separate processes in various vertebrates, including humans.[1] Prolactin is secreted from the pituitary gland in response to eating, mating, estrogen treatment, ovulation and nursing. Prolactin is secreted in pulses in between these events. Prolactin plays an essential role in metabolism, regulation of the immune system and pancreatic development.

Discovered in non-human animals around 1930 by Oscar Riddle[2] and confirmed in humans in 1970 by Henry Friesen[3] prolactin is a peptide hormone, encoded by the PRL gene.[4]

In mammals, prolactin is associated with milk production; in fish it is thought to be related to the control of water and salt balance. Prolactin also acts in a cytokine-like manner and as an important regulator of the immune system. It has important cell cycle-related functions as a growth-, differentiating- and anti-apoptotic factor. As a growth factor, binding to cytokine-like receptors, it influences hematopoiesis, angiogenesis and is involved in the regulation of blood clotting through several pathways. The hormone acts in endocrine, autocrine and paracrine manner through the prolactin receptor and a large number of cytokine receptors.[1]

Pituitary prolactin secretion is regulated by endocrine neurons in the hypothalamus. The most important of these are the neurosecretory tuberoinfundibulum (TIDA) neurons of the arcuate nucleus that secrete dopamine (aka Prolactin Inhibitory Hormone) to act on the D2 receptors of lactotrophs, causing inhibition of prolactin secretion. Thyrotropin-releasing factor (thyrotropin-releasing hormone) has a stimulatory effect on prolactin release, however prolactin is the only adenohypophyseal hormone whose principal control is inhibitory.

Several variants and forms are known per species. Many fish have variants prolactin A and prolactin B. Most vertebrates including humans also have the closely related somatolactin. In humans, three smaller (4, 16 and 22 kDa) and several larger (so called big and big-big) variants exist.[not verified in body]

Functions

Prolactin has a wide variety of effects. It stimulates the mammary glands to produce milk (lactation): increased serum concentrations of prolactin during pregnancy cause enlargement of the mammary glands and prepare for milk production, which normally starts when levels of progesterone fall by the end of pregnancy and a suckling stimulus is present. Prolactin plays an important role in maternal behavior.[5]

The hormone counteracts the effect of dopamine.[citation needed]

Elevated levels of prolactin decrease the levels of sex hormones — estrogen in women and testosterone in men.[6] The effects of mildly elevated levels of prolactin are much more variable, in women, substantially increasing or decreasing estrogen levels.

Prolactin is sometimes classified as a gonadotropin[7] although in humans it has only a weak luteotropic effect while the effect of suppressing classical gonadotropic hormones is more important.[8] Prolactin within the normal reference ranges can act as a weak gonadotropin, but at the same time suppresses GnRH secretion. The exact mechanism by which it inhibits GnRH is poorly understood. Although expression of prolactin receptors (PRL-R) have been demonstrated in rat hypothalamus, the same has not been observed in GnRH neurons.[9] Physiologic levels of prolactin in males enhance luteinizing hormone-receptors in Leydig cells, resulting in testosterone secretion, which leads to spermatogenesis.[10]

Prolactin also stimulates proliferation of oligodendrocyte precursor cells. These cells differentiate into oligodendrocytes, the cells responsible for the formation of myelin coatings on axons in the central nervous system.[11]

Other actions include contributing to pulmonary surfactant synthesis of the fetal lungs at the end of the pregnancy and immune tolerance of the fetus by the maternal organism during pregnancy. Prolactin promotes neurogenesis in maternal and fetal brains.[12][13]

Functions in other vertebrate species

The primary function of prolactin in fish is osmoregulation[14], i.e., controlling the movement of water and salts between the tissues of the fish and the surrounding water. Like mammals, however, prolactin in fish also has reproductive functions, including promoting sexual maturation and inducing breeding cycles, as well as brooding and parental care.[15] In the South American discus, prolactin may also regulate the production of a skin secretion that provides food for larval fry.[16] An increase in brooding behaviour caused by prolactin has been reported in hens.[17]

Prolactin and its receptor are expressed in the skin, specifically in the hair follicles, where they regulate hair growth and moulting in an autocrine fashion.[18][19] Elevated levels of prolactin can inhibit hair growth[20], and knock-out mutations in the prolactin gene cause increased hair length in cattle[21] and mice.[19] Conversely, mutations in the prolactin receptor can cause reduced hair growth, resulting in the "slick" phenotype in cattle.[21][22] Additionally, prolactin delays hair regrowth in mice.[23]

Analogous to its effects on hair growth and shedding in mammals, prolactin in birds controls the moulting of feathers,[24] as well as the age at onset of feathering in both turkeys and chickens.[25]

Regulation

In humans, prolactin is produced at least in the anterior pituitary, decidua, myometrium, breast, lymphocytes, leukocytes and prostate.[26][27]

Pituitary PRL is controlled by the Pit-1 transcription factor that binds to the prolactin gene at several sites. Ultimately dopamine, extrapituitary PRL is controlled by a superdistal promoter and apparently unaffected by dopamine.[27] The thyrotropin-releasing hormone and the vasoactive intestinal peptide stimulate the secretion of prolactin in experimental settings, however their physiological influence is unclear. The main stimulus for prolactin secretion is suckling, the effect of which is neuronally mediated.[28] A key regulator of prolactin production is estrogens that enhance growth of prolactin-producing cells and stimulate prolactin production directly, as well as suppressing dopamine.

In decidual cells and in lymphocytes the distal promoter and thus prolactin expression is stimulated by cAMP. Responsivness to cAMP is mediated by an imperfect cAMP–responsive element and two CAAT/enhancer binding proteins (C/EBP).[27] Progesterone upregulates prolactin synthesis in the endometrium and decreases it in myometrium and breast glandular tissue.[29] Breast and other tissues may express the Pit-1 promoter in addition to the distal promoter.

Extrapituitary production of prolactin is thought to be special to humans and primates and may serve mostly tissue-specific paracrine and autocrine purposes. It has been hypothesized that in vertebrates such as mice a similar tissue-specific effect is achieved by a large family of prolactin-like proteins controlled by at least 26 paralogous PRL genes not present in primates.[27]

Vasoactive intestinal peptide and peptide histidine isoleucine help to regulate prolactin secretion in humans, but the functions of these hormones in birds can be quite different.[30]

Prolactin follows diurnal and ovulatory cycles. Prolactin levels peak during REM sleep and in the early morning. Many mammals experience a seasonal cycle.

During pregnancy, high circulating concentrations of estrogen and progesterone increase prolactin levels by 10- to 20-fold. Estrogen and progesterone inhibit the stimulatory effects of prolactin on milk production. The abrupt drop of estrogen and progesterone levels following delivery allow prolactin—which temporarily remains high—to induce lactation.[verification needed]

Sucking on the nipple offsets the fall in prolactin as the internal stimulus for them is removed. The sucking activates mechanoreceptors in and around the nipple. These signals are carried by nerve fibers through the spinal cord to the hypothalamus, where changes in the electrical activity of neurons that regulate the pituitary gland increase prolactin secretion. The suckling stimulus also triggers the release of oxytocin from the posterior pituitary gland, which triggers milk let-down: Prolactin controls milk production (lactogenesis) but not the milk-ejection reflex; the rise in prolactin fills the breast with milk in preparation for the next feed.

In usual circumstances, in the absence of galactorrhea, lactation ceases within one or two weeks following the end of breastfeeding.

Levels can rise after exercise, high-protein meals, minor surgical procedures,[31] following epileptic seizures[32] or due to physical or emotional stress.[33][34] In a study on female volunteers under hypnosis, prolactin surges resulted from the evocation, with rage, of humiliating experiences, but not from the fantasy of nursing.[34]

Prolactin levels have also been found to rise with use of the drug MDMA.[35]

Hypersecretion is more common than hyposecretion. Hyperprolactinemia is the most frequent abnormality of the anterior pituitary tumors, termed prolactinomas. Prolactinomas may disrupt the hypothalamic-pituitary-gonadal axis as prolactin tends to suppress the secretion of GnRH from the hypothalamus and in turn decreases the secretion of follicle-stimulating hormone (FSH) and luteinizing hormone (LH) from the anterior pituitary, therefore disrupting the ovulatory cycle.[36] Such hormonal changes may manifest as amenorrhea and infertility in females as well as impotence in males. Inappropriate lactation (galactorrhoea) is another important clinical sign of prolactinomas.

Structure and isoforms

The structure of prolactin is similar to that of growth hormone and placental lactogen. The molecule is folded due to the activity of three disulfide bonds. Significant heterogeneity of the molecule has been described, thus bioassays and immunoassays can give different results due to differing glycosylation, phosphorylation and sulfation, as well as degradation. The non-glycosylated form of prolactin is the dominant form that is secreted by the pituitary gland.

The three different sizes of prolactin are:

  • Little prolactin—the predominant form.[37] It has a molecular weight of appxoximately 22-kDa.[37] It is a single-chain polypeptide of 198 amino acids and is apparently the result of removal of some amino acids.
  • Big prolactin—approximately 48 kDa.[37] It may be the product of interaction of several prolactin molecules. It appears to have little, if any, biological activity.[38]
  • Big big prolactin—approximately 150 kDa.[37] It appears to have a low biological activity.[39]

The levels of larger ones are somewhat higher during the early postpartum period.[40]

Prolactin receptor

Main article: Prolactin receptor

Prolactin receptors are present in the mammillary glands, ovaries, pituitary glands, heart, lung, thymus, spleen, liver, pancreas, kidney, adrenal gland, uterus, skeletal muscle, skin and areas of the central nervous system.[41] When prolactin binds to the receptor, it causes it to dimerize with another prolactin receptor. This results in the activation of Janus kinase 2, a tyrosine kinase that initiates the JAK-STAT pathway. Activation also results in the activation of mitogen-activated protein kinases and Src kinase.[41]

Human prolactin receptors are insensitive to mouse prolactin.[42]

Diagnostic use

Prolactin levels may be checked as part of a sex hormone workup, as elevated prolactin secretion can suppress the secretion of FSH and GnRH, leading to hypogonadism and sometimes causing erectile dysfunction.

Prolactin levels may be of some use in distinguishing epileptic seizures from psychogenic non-epileptic seizures. The serum prolactin level usually rises following an epileptic seizure.[43]

Units and unit conversions

The serum concentration of prolactin can be given in mass concentration (µg/L or ng/mL), molar concentration (nmol/L or pmol/L) or in international units (typically mIU/L). The current IU is calibrated against the third International Standard for Prolactin, IS 84/500.[44][45] Reference ampoules of IS 84/500 contain 2.5 µg of lyophilized human prolactin[46] and have been assigned an activity of .053 International Units.[44][45] Measurements that are calibrated against the current international standard can be converted into mass units using this ratio of grams to IUs;[47] prolactin concentrations expressed in mIU/L can be converted to µg/L by dividing by 21.2. Previous standards use other ratios.[48][49][50][51]

The first International Reference Preparation (or IRP) of human Prolactin for Immunoassay was established in 1978 (75/504 1st IRP for human Prolactin) at a time when purified human prolactin was in short supply.[47][48] Previous standards relied on prolactin from animal sources.[51] Purified human prolactin was scarce, heterogeneous, unstable and difficult to characterize. A preparation labelled 81/541 was distributed by the WHO Expert Committee on Biological Standardization without official status and given the assigned value of 50 mIU/ampoule based on an earlier collaborative study.[47][49] It was determined that this preparation behaved anomalously in certain immunoassays and was not suitable as an IS.[47]

Three different human pituitary extracts containing prolactin were subsequently obtained as candidates for an IS. These were distributed into ampoules coded 83/562, 83/573 and 84/500.[44][45][47][50] Collaborative studies involving 20 different laboratories found little difference between these three preparations. 83/562 appeared to be the most stable. This preparation was largely free of dimers and polymers of prolactin. On the basis of these investigations 83/562 was established as the Second IS for human Prolactin.[50] Once stocks of these ampoules were depleted, 84/500 was established as the Third IS for human Prolactin.[44][47]

Reference ranges

General guidelines for diagnosing prolactin excess (hyperprolactinemia) define the upper threshold of normal prolactin at 25 µg/L for women and 20 µg/L for men.[41] Similarly, guidelines for diagnosing prolactin deficiency (hypoprolactinemia) are defined as prolactin levels below 3 µg/L in women[52][53] and 5 µg/L in men.[54][55][56] However, different assays and methods for measuring prolactin are employed by different laboratories and as such the serum reference range for prolactin is often determined by the laboratory performing the measurement.[41][57] Furthermore, prolactin levels also vary factors including age,[58] sex,[58] menstrual cycle stage[58] and pregnancy.[58] The circumstances surrounding a given prolactin measurement (assay, patient condition, etc.) must therefore be considered before the measurement can be accurately interpreted.[41]

The following chart illustrates the variations seen in normal prolactin measurements across different populations. Prolactin values were obtained from specific control groups of varying sizes using the IMMULITE assay.[58]

Typical prolactin values
Proband Prolactin, µg/L
women, follicular phase (n = 803)
12.1
women, luteal phase (n = 699)
13.9
women, mid-cycle (n = 53)
17
women, whole cycle (n = 1555)
13.0
women, pregnant, 1st trimester (n = 39)
16
women, pregnant, 2nd trimester (n = 52)
49
women, pregnant, 3rd trimester (n = 54)
113
Men, 21–30 (n = 50)
9.2
Men, 31–40 (n = 50)
7.1
Men, 41–50 (n = 50)
7.0
Men, 51–60 (n = 50)
6.2
Men, 61–70 (n = 50)
6.9

Inter-method variability

The following table illustrates variability in reference ranges of serum prolactin between some commonly used assay methods (as of 2008), using a control group of healthy health care professionals (53 males, age 20–64 years, median 28 years; 97 females, age 19–59 years, median 29 years) in Essex, England:[57]

Assay method Mean
Prolactin		 Lower limit
2.5th percentile		 Upper limit
97.5th percentile
µg/L mIU/L µg/L mIU/L µg/L mIU/L
Females
Centaur 7.92 168 3.35 71 16.4 348
Immulite 9.25 196 3.54 75 18.7 396
Access 9.06 192 3.63 77 19.3 408
AIA 9.52[59] 257[59] 3.89[59] 105[59] 20.3[59] 548[59]
Elecsys 10.5 222 4.15 88 23.2 492
Architect 10.6 225 4.62 98 21.1 447
Males
Access 6.89 146 2.74 58 13.1 277
Centaur 7.88 167 2.97 63 12.4 262
Immulite 7.45 158 3.30 70 13.3 281
AIA 7.81[59] 211[59] 3.30[59] 89[59] 13.5[59] 365[59]
Elecsys 8.49 180 3.40 72 15.6 331
Architect 8.87 188 4.01 85 14.6 310

An example usage of table above is, if using the Centaur assay to estimate prolactin values in µg/L for females, the mean is 7.92 µg/L and the reference range is 3.35–16.4 µg/L.

Conditions

Elevated levels

Hyperprolactinaemia, or excess serum prolactin, is associated with hypoestrogenism, anovulatory infertility, oligomenorrhoea, amenorrhoea, unexpected lactation and loss of libido in women and erectile dysfunction and loss of libido in men.[60]

Decreased levels

Main article: Hypoprolactinemia

Hypoprolactinemia, or serum prolactin deficiency, is associated with ovarian dysfunction in women,[52][53] and arteriogenic erectile dysfunction, premature ejaculation,[54] oligozoospermia, asthenospermia, hypofunction of seminal vesicles and hypoandrogenism[55] in men. In one study, normal sperm characteristics were restored when prolactin levels were raised to normal values in hypoprolactinemic men.[56]

Hypoprolactinemia can result from hypopituitarism, excessive dopaminergic action in the tuberoinfundibular pathway and ingestion of D2 receptor agonists such as bromocriptine.

While there is evidence that women who smoke tend to breast feed for shorter periods, there is a wide variation of breast-feeding rates in women who do smoke. This suggest that psychosocial factors rather than physiological mechanisms (e.g., nicotine suppressing prolactin levels) are responsible for the lower rates of breast feeding in women who do smoke.[61][62]

In medicine

Prolactin is available commercially for use in animals, but not in humans.[63] It is used to stimulate lactation in animals.[63] The biological half-life of prolactin in humans is around 15–20 minutes.[64] The D2 receptor is involved in the regulation of prolactin secretion, and agonists of the receptor such as bromocriptine and cabergoline decrease prolactin levels while antagonists of the receptor such as domperidone, metoclopramide, haloperidol, risperidone, and sulpiride increase prolactin levels.[65] D2 receptor antagonists like domperidone, metoclopramide, and sulpiride are used as galactogogues to increase prolatin secretion in pituitary gland and induce lactation in humans.[66]

See also

References

  1. ↑ 1.0 1.1 Bole-Feysot C, Goffin V, Edery M, Binart N, Kelly PA (Jun 1998). "Prolactin (PRL) and its receptor: actions, signal transduction pathways and phenotypes observed in PRL receptor knockout mice". Endocrine Reviews. 19 (3): 225–68. doi:10.1210/er.19.3.225. PMID 9626554.
  2. ↑ Bates R, Riddle O (November 1935). "The preparation of prolactin". Journal of Pharmacology and Experimental Therapeutics. 55 (3): 365–371.
  3. ↑ Friesen H, Guyda H, Hardy J (Dec 1970). "The biosynthesis of human growth hormone and prolactin". The Journal of Clinical Endocrinology and Metabolism. 31 (6): 611–24. doi:10.1210/jcem-31-6-611. PMID 5483096.
  4. ↑ Evans AM, Petersen JW, Sekhon GS, DeMars R (May 1989). "Mapping of prolactin and tumor necrosis factor-beta genes on human chromosome 6p using lymphoblastoid cell deletion mutants". Somatic Cell and Molecular Genetics. 15 (3): 203–13. doi:10.1007/BF01534871. PMID 2567059.
  5. ↑ Lucas BK, Ormandy CJ, Binart N, Bridges RS, Kelly PA (Oct 1998). "Null mutation of the prolactin receptor gene produces a defect in maternal behavior". Endocrinology. 139 (10): 4102–7. doi:10.1210/endo.139.10.6243. PMID 9751488.
  6. ↑ Prolactinoma—Mayo Clinic
  7. ↑ Hoehn K, Marieb EN (2007). Human Anatomy & Physiology. San Francisco: Pearson Benjamin Cummings. p. 605. ISBN 0-8053-5909-5.
  8. ↑ Gonadotropins at the US National Library of Medicine Medical Subject Headings (MeSH)
  9. ↑ Grattan DR, Jasoni CL, Liu X, Anderson GM, Herbison AE (Sep 2007). "Prolactin regulation of gonadotropin-releasing hormone neurons to suppress luteinizing hormone secretion in mice". Endocrinology. 148 (9): 4344–51. doi:10.1210/en.2007-0403. PMID 17569755.
  10. ↑ Hair WM, Gubbay O, Jabbour HN, Lincoln GA (Jul 2002). "Prolactin receptor expression in human testis and accessory tissues: localization and function". Molecular Human Reproduction. 8 (7): 606–11. doi:10.1093/molehr/8.7.606. PMID 12087074.
  11. ↑ Gregg C, Shikar V, Larsen P, Mak G, Chojnacki A, Yong VW, Weiss S (Feb 2007). "White matter plasticity and enhanced remyelination in the maternal CNS". The Journal of Neuroscience. 27 (8): 1812–23. doi:10.1523/JNEUROSCI.4441-06.2007. PMID 17314279.
  12. ↑ Shingo T, Gregg C, Enwere E, Fujikawa H, Hassam R, Geary C, Cross JC, Weiss S (Jan 2003). "Pregnancy-stimulated neurogenesis in the adult female forebrain mediated by prolactin". Science. 299 (5603): 117–20. doi:10.1126/science.1076647. PMID 12511652.
  13. ↑ Larsen CM, Grattan DR (Feb 2012). "Prolactin, neurogenesis, and maternal behaviors". Brain, Behavior, and Immunity. 26 (2): 201–9. doi:10.1016/j.bbi.2011.07.233. PMID 21820505.
  14. ↑ Sakamoto T, McCormick SD (May 2006). "Prolactin and growth hormone in fish osmoregulation". General and Comparative Endocrinology. 147 (1): 24–30. doi:10.1016/j.ygcen.2005.10.008. PMID 16406056.
  15. ↑ Whittington CM, Wilson AB (September 2013). "The role of prolactin in fish reproduction". General and Comparative Endocrinology. 191: 123–36. doi:10.1016/j.ygcen.2013.05.027. PMID 23791758.
  16. ↑ Khong HK, Kuah MK, Jaya-Ram A, Shu-Chien AC (May 2009). "Prolactin receptor mRNA is upregulated in discus fish (Symphysodon aequifasciata) skin during parental phase". Comparative Biochemistry and Physiology Part B: Biochemistry and Molecular Biology. 153 (1): 18–28. doi:10.1016/j.cbpb.2009.01.005. PMID 19272315.
  17. ↑ Jiang RS, Xu GY, Zhang XQ, Yang N (June 2005). "Association of polymorphisms for prolactin and prolactin receptor genes with broody traits in chickens". Poltry Science. 84 (6): 839–845. doi:10.1093/ps/84.6.839. PMID 15971519.
  18. ↑ Foitzik K, Krause K, Nixon AJ, Ford CA, Ohnemus U, Pearson AJ, Paus R (May 2003). "Prolactin and Its Receptor Are Expressed in Murine Hair Follicle Epithelium, Show Hair Cycle-Dependent Expression, and Induce Catagen". The American Journal of Pathology. 162 (5): 1611–21. doi:10.1016/S0002-9440(10)64295-2. PMC 1851183. PMID 12707045.
  19. ↑ 19.0 19.1 Craven AJ, Ormandy CJ, Robertson FG, Wilkins RJ, Kelly PA, Nixon AJ, Pearson AJ (June 2001). "Prolactin Signaling Influences the Timing Mechanism of the Hair Follicle: Analysis of Hair Growth Cycles in Prolactin Receptor Knockout Mice". Endocrinology. 142 (6): 2533–9. doi:10.1210/endo.142.6.8179. PMID 11356702.
  20. ↑ Foitzik K, Krause K, Conrad F, Nakamura M, Funk W, Paus R (March 2006). "Human scalp hair follicles are both a target and a source of prolactin, which serves as an autocrine and/or paracrine promoter of apoptosis-driven hair follicle regression". The American Journal of Pathology. 168 (3): 748–56. doi:10.2353/ajpath.2006.050468. PMC 1606541. PMID 16507890.
  21. ↑ 21.0 21.1 Littlejohn MD, Henty KM, Tiplady K, Johnson T, Harland C, Lopdell T, Sherlock RG, Li W, Lukefahr SD, Shanks BC, Garrick DJ, Snell RG, Spelman RJ, Davis SR (December 2014). "Functionally reciprocal mutations of the prolactin signalling pathway define hairy and slick cattle". Nature Communications. 5: 5861. doi:10.1038/ncomms6861. PMC 4284646. PMID 25519203.
  22. ↑ Porto-Neto LR, Bickhart DM, Landaeta-Hernandez AJ, Utsunomiya YT, Pagan M, Jimenez E, Hansen PJ, Dikmen S, Schroeder SG, Kim ES, Sun J, Crespo E, Amati N, Cole JB, Null DJ, Garcia JF, Reverter A, Barendse W, Sonstegard TS (February 2018). "Convergent Evolution of Slick Coat in Cattle through Truncation Mutations in the Prolactin Receptor". Frontiers in Genetics. 9: 57. doi:10.3389/fgene.2018.00057. PMC 5829098. PMID 29527221.
  23. ↑ Craven AJ, Nixon AJ, Ashby MG, Ormandy CJ, Blazek K, Wilkins RJ, Pearson AJ (Nov 2006). "Prolactin delays hair regrowth in mice". The Journal of Endocrinology. 191 (2): 415–25. doi:10.1677/joe.1.06685. PMID 17088411.
  24. ↑ Dawson A (July 2006). "Control of molt in birds: association with prolactin and gonadal regression in starlings". General and Comparative Endocrinology. 147 (3): 314–22. doi:10.1016/j.ygcen.2006.02.001. PMID 16530194.
  25. ↑ Derks MF, Herrero-Medrano JM, Crooijmans RP, Vereijken A, Long JA, Megens HJ, Groenen MA (February 2018). "Early and late feathering in turkey and chicken: same gene but different mutations". Genetics Selection Evolution. 50: 7. doi:10.1186/s12711-018-0380-3. PMC 5863816. PMID 29566646.
  26. ↑ Ben-Jonathan N, Mershon JL, Allen DL, Steinmetz RW (Dec 1996). "Extrapituitary prolactin: distribution, regulation, functions, and clinical aspects". Endocrine Reviews. 17 (6): 639–69. doi:10.1210/edrv-17-6-639. PMID 8969972.
  27. ↑ 27.0 27.1 27.2 27.3 Gerlo S, Davis JR, Mager DL, Kooijman R (Oct 2006). "Prolactin in man: a tale of two promoters". BioEssays. 28 (10): 1051–5. doi:10.1002/bies.20468. PMC 1891148. PMID 16998840.
  28. ↑ Norman AW, Henry HL, eds. (2014). "III. Structure, Synthesis, Secretion, and Target Cells of the Hypothalamic Releasing Hormones: E. Hypothalamic Control of Prolactin Secretion". Hormones. Academic Press. p. 66. ISBN 9780080919065.
  29. ↑ Zinger M, McFarland M, Ben-Jonathan N (Feb 2003). "Prolactin expression and secretion by human breast glandular and adipose tissue explants". The Journal of Clinical Endocrinology and Metabolism. 88 (2): 689–96. doi:10.1210/jc.2002-021255. PMID 12574200.
  30. ↑ Kulick RS, Chaiseha Y, Kang SW, Rozenboim I, El Halawani ME (Jul 2005). "The relative importance of vasoactive intestinal peptide and peptide histidine isoleucine as physiological regulators of prolactin in the domestic turkey". General and Comparative Endocrinology. 142 (3): 267–73. doi:10.1016/j.ygcen.2004.12.024. PMID 15935152.
  31. ↑ Melmed S, Jameson JL (2005). "333 Disorders of the Anterior Pituitary and Hypothalamus". In Jameson JN, Kasper DL, Harrison TR, Braunwald E, Fauci AS, Hauser SL, Longo DL. Harrison's principles of internal medicine (16th ed.). New York: McGraw-Hill Medical Publishing Division. ISBN 0-07-140235-7.
  32. ↑ Mellers JD (Aug 2005). "The approach to patients with "non-epileptic seizures"". Postgraduate Medical Journal. 81 (958): 498–504. doi:10.1136/pgmj.2004.029785. PMC 1743326. PMID 16085740.
  33. ↑ "Prolactin". MedLine plus. Retrieved 2014-10-24.
  34. ↑ 34.0 34.1 Sobrinho LG (2003). "Prolactin, psychological stress and environment in humans: adaptation and maladaptation". Pituitary. 6 (1): 35–9. doi:10.1023/A:1026229810876. PMID 14674722.
  35. ↑ Passie T, Hartmann U, Schneider U, Emrich HM, Krüger TH (2005). "Ecstasy (MDMA) mimics the post-orgasmic state: impairment of sexual drive and function during acute MDMA-effects may be due to increased prolactin secretion". Med Hypotheses. 64 (5): 899–903. doi:10.1016/j.mehy.2004.11.044. PMID 15780482.
  36. ↑ "Etiology, diagnosis, and treatment of secondary amenorrhea". Retrieved 7 November 2013.
  37. ↑ 37.0 37.1 37.2 37.3 Sabharwal P, Glaser R, Lafuse W, Varma S, Liu Q, Arkins S, Kooijman R, Kutz L, Kelley KW, Malarkey WB (Aug 1992). "Prolactin synthesized and secreted by human peripheral blood mononuclear cells: an autocrine growth factor for lymphoproliferation". Proceedings of the National Academy of Sciences of the United States of America. 89 (16): 7713–6. doi:10.1073/pnas.89.16.7713. PMC 49781. PMID 1502189., in turn citing: Kiefer KA, Malarkey WB (Jan 1978). "Size heterogeneity of human prolactin in CSF and serum: experimental conditions that alter gel filtration patterns". The Journal of Clinical Endocrinology and Metabolism. 46 (1): 119–24. doi:10.1210/jcem-46-1-119. PMID 752015.
  38. ↑ Garnier PE, Aubert ML, Kaplan SL, Grumbach MM (Dec 1978). "Heterogeneity of pituitary and plasma prolactin in man: decreased affinity of "Big" prolactin in a radioreceptor assay and evidence for its secretion". The Journal of Clinical Endocrinology and Metabolism. 47 (6): 1273–81. doi:10.1210/jcem-47-6-1273. PMID 263349.
  39. ↑ Leite V, Cosby H, Sobrinho LG, Fresnoza MA, Santos MA, Friesen HG (Oct 1992). "Characterization of big, big prolactin in patients with hyperprolactinaemia". Clinical Endocrinology. 37 (4): 365–72. doi:10.1111/j.1365-2265.1992.tb02340.x. PMID 1483294.
  40. ↑ Kamel MA, Neulen J, Sayed GH, Salem HT, Breckwoldt M (Sep 1993). "Heterogeneity of human prolactin levels in serum during the early postpartum period". Gynecological Endocrinology. 7 (3): 173–7. doi:10.3109/09513599309152499. PMID 8291454.
  41. ↑ 41.0 41.1 41.2 41.3 41.4 Mancini T, Casanueva FF, Giustina A (Mar 2008). "Hyperprolactinemia and prolactinomas". Endocrinology and Metabolism Clinics of North America. 37 (1): 67–99, viii. doi:10.1016/j.ecl.2007.10.013. PMID 18226731.
  42. ↑ Utama FE, LeBaron MJ, Neilson LM, Sultan AS, Parlow AF, Wagner KU, Rui H (Mar 2006). "Human prolactin receptors are insensitive to mouse prolactin: implications for xenotransplant modeling of human breast cancer in mice". The Journal of Endocrinology. 188 (3): 589–601. doi:10.1677/joe.1.06560. PMID 16522738.
  43. ↑ Banerjee S, Paul P, Talib VJ (Aug 2004). "Serum prolactin in seizure disorders". Indian Pediatrics. 41 (8): 827–31. PMID 15347871.
  44. ↑ 44.0 44.1 44.2 44.3 Schulster D, Gaines Das RE, Jeffcoate SL (Apr 1989). "International Standards for human prolactin: calibration by international collaborative study". The Journal of Endocrinology. 121 (1): 157–66. doi:10.1677/joe.0.1210157. PMID 2715755.
  45. ↑ 45.0 45.1 45.2 "WHO Expert Committee on Biological Standardization" (PDF). Thirty-ninth Report, WHO Technical Report Series. World Health Organization. 1989. Retrieved 2009-06-03. 86.1520, WHO/BS documents: 86.1520 Add 1, 88.1596
  46. ↑ "WHO International Standard, Prolactin, Human. NIBSC code: 84/500, Instructions for use" (PDF). WHO International Standard, Prolactin, Human. NIBSC code: 84/500, Instructions for use. NIBSC / Health Protection Agency. 1989. Archived from the original (PDF) on 2011-10-03. Retrieved 2011-03-21.
  47. ↑ 47.0 47.1 47.2 47.3 47.4 47.5 Canadian Society of Clinical Chemists (Dec 1992). "Canadian Society of Clinical Chemists position paper: standardization of selected polypeptide hormone measurements". Clinical Biochemistry. 25 (6): 415–24. doi:10.1016/0009-9120(92)90030-V. PMID 1477965.
  48. ↑ 48.0 48.1 Gaines Das RE, Cotes PM (Jan 1979). "International Reference Preparation of human prolactin for immunoassay: definition of the International Unit, report of a collaborative study and comparison of estimates of human prolactin made in various laboratories". The Journal of Endocrinology. 80 (1): 157–68. doi:10.1677/joe.0.0800157. PMID 429949.
  49. ↑ 49.0 49.1 "WHO Expert Committee on Biological Standardization" (PDF). Thirty-fifth Report, WHO Technical Report Series. World Health Organization. 1985. Retrieved 2011-03-21.
  50. ↑ 50.0 50.1 50.2 "WHO Expert Committee on Biological Standardization" (PDF). Thirty-seventh Report, WHO Technical Report Series. World Health Organization. 1987. Retrieved 2011-03-21.
  51. ↑ 51.0 51.1 Bangham DR, Mussett MV, Stack-Dunne MP (1963). "THE SECOND INTERNATIONAL STANDARD FOR PROLACTIN". Bulletin of the World Health Organization. 29 (6): 721–8. PMC 2555104. PMID 14107744.
  52. ↑ 52.0 52.1 Kauppila A, Martikainen H, Puistola U, Reinilä M, Rönnberg L (Mar 1988). "Hypoprolactinemia and ovarian function". Fertility and Sterility. 49 (3): 437–41. doi:10.1016/s0015-0282(16)59769-6. PMID 3342895.
  53. ↑ 53.0 53.1 Schwärzler P, Untergasser G, Hermann M, Dirnhofer S, Abendstein B, Berger P (Oct 1997). "Prolactin gene expression and prolactin protein in premenopausal and postmenopausal human ovaries". Fertility and Sterility. 68 (4): 696–701. doi:10.1016/S0015-0282(97)00320-8. PMID 9341613.
  54. ↑ 54.0 54.1 Corona G, Mannucci E, Jannini EA, Lotti F, Ricca V, Monami M, Boddi V, Bandini E, Balercia G, Forti G, Maggi M (May 2009). "Hypoprolactinemia: a new clinical syndrome in patients with sexual dysfunction". The Journal of Sexual Medicine. 6 (5): 1457–66. doi:10.1111/j.1743-6109.2008.01206.x. PMID 19210705.
  55. ↑ 55.0 55.1 Gonzales GF, Velasquez G, Garcia-Hjarles M (1989). "Hypoprolactinemia as related to seminal quality and serum testosterone". Archives of Andrology. 23 (3): 259–65. doi:10.3109/01485018908986849. PMID 2619414.
  56. ↑ 56.0 56.1 Ufearo CS, Orisakwe OE (Sep 1995). "Restoration of normal sperm characteristics in hypoprolactinemic infertile men treated with metoclopramide and exogenous human prolactin". Clinical Pharmacology and Therapeutics. 58 (3): 354–9. doi:10.1016/0009-9236(95)90253-8. PMID 7554710.
  57. ↑ 57.0 57.1 Table 2 in Beltran L, Fahie-Wilson MN, McKenna TJ, Kavanagh L, Smith TP (Oct 2008). "Serum total prolactin and monomeric prolactin reference intervals determined by precipitation with polyethylene glycol: evaluation and validation on common immunoassay platforms". Clinical Chemistry. 54 (10): 1673–81. doi:10.1373/clinchem.2008.105312. PMID 18719199.
  58. ↑ 58.0 58.1 58.2 58.3 58.4 Prolaktin Archived 28 July 2011 at the Wayback Machine. at medical.siemens.com—reference ranges as determined from the IMMULITE assay method
  59. ↑ 59.00 59.01 59.02 59.03 59.04 59.05 59.06 59.07 59.08 59.09 59.10 59.11 The AIA essay values are also from Table 2 in Beltran 2008, like the other values, but it uses a different conversion factor of 27.0 mIU/L per µg/L, taken from the second international standard, IS 83/562).
  60. ↑ Melmed S, Kleinberg D 2008 Anterior pituitary. 1n: Kronenberg HM, Melmed S, Polonsky KS, Larsen PR, eds. Willams textbook of endocrinology. 11th ed. Philadelphia: Saunders Elsevier; 185-261
  61. ↑ Amir LH (2001). "Maternal smoking and reduced duration of breastfeeding: a review of possible mechanisms". Early Human Development. 64 (1): 45–67. doi:10.1016/S0378-3782(01)00170-0. PMID 11408108.
  62. ↑ Amir LH, Donath SM (2002). "Does maternal smoking have a negative physiological effect on breastfeeding? The epidemiological evidence". Birth (Berkeley, Calif.). 29 (2): 112–23. doi:10.1046/j.1523-536X.2002.00152.x. PMID 12000412.
  63. ↑ 63.0 63.1 Coutts RT, Smail GA (12 May 2014). Polysaccharides Peptides and Proteins: Pharmaceutical Monographs. Elsevier. pp. 153–. ISBN 978-1-4831-9612-1.
  64. ↑ D.F. Horrobin (6 December 2012). Prolactin: Physiology and Clinical Significance. Springer Science & Business Media. pp. 13–. ISBN 978-94-010-9695-9.
  65. ↑ Martin H. Johnson (14 December 2012). Essential Reproduction. John Wiley & Sons. pp. 40–. ISBN 978-1-118-42388-2.
  66. ↑ Jan Riordan (January 2005). Breastfeeding and Human Lactation. Jones & Bartlett Learning. pp. 468–. ISBN 978-0-7637-4585-1.

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