Hypogonadism pathophysiology: Difference between revisions
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|FGF8<ref name="pmid18596921">{{cite journal| author=Falardeau J, Chung WC, Beenken A, Raivio T, Plummer L, Sidis Y et al.| title=Decreased FGF8 signaling causes deficiency of gonadotropin-releasing hormone in humans and mice. | journal=J Clin Invest | year= 2008 | volume= 118 | issue= 8 | pages= 2822-31 | pmid=18596921 | doi=10.1172/JCI34538 | pmc=2441855 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=18596921 }}</ref> | |FGF8<ref name="pmid18596921">{{cite journal| author=Falardeau J, Chung WC, Beenken A, Raivio T, Plummer L, Sidis Y et al.| title=Decreased FGF8 signaling causes deficiency of gonadotropin-releasing hormone in humans and mice. | journal=J Clin Invest | year= 2008 | volume= 118 | issue= 8 | pages= 2822-31 | pmid=18596921 | doi=10.1172/JCI34538 | pmc=2441855 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=18596921 }}</ref> | ||
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* Deafness | * Deafness | ||
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|PROK2 | |PROK2 | ||
PROKR2 | PROKR2 | ||
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Revision as of 20:30, 20 July 2017
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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1] Associate Editor(s)-in-Chief: Ahmed Elsaiey, MBBCH [2]
Overview
Pathophysiology
Pathogenesis
Hypogonadism in males
- The hypogonadism pathogenesis in males depends mainly on the testosterone deficiency. Testosterone secretion occurs as the following:
- Testosterone is secreted in response to stimulation signals from the brain cortex to the hypothalamus. The hypothalamus by its role secrets the gonadotropin releasing hormones (GnRH).
- GnRH stimulates the pituitary gland which by its role secretes the gonadal hormones the Follicle Stimulating Hormone (FSH) and the Luteinizing Hormone (LH).
- In males, LH stimulates the leydig cells in the testes which produce testosterone by converting the cholesterol to testosterone.
- Production of testosterone from the testes gives negative feed back to the pituitary. This feedback inhibit the production of FSH and LH from the pituitary.
- Testosterone deficiency can occur when different acquired or congenital disease affect the organs responsible for its secretion. So, pathogenesis of the hypogonadism in males depends on the underlying cause.[1]
- GnRH deficiency has a main role in hypogonadism pathogenesis in males as it leads to decrease of the gonadal hormone and deficiency of testosterone eventually.[2]
- It has been proved that GnRH deficiency is associated with most cases of idiopathic hypogonadotrophic hypogonadism in males.
Genetic
- Gentic mutations have a big role in development of the hypogonadism especially congenital hypogonadotropic hypogonadism. There are more than 25 genes participate in the pathogenesis of hypogonadism.[3]
- In this table number of genes with the associated diseases causing hypogonadism are enlisted:
| Associated disease | Genes | Mutation | Associated features with the mutated gene | Comments |
|---|---|---|---|---|
| Kalman syndrome (With loss of smelling sense - Anosmia) | ANOS 1[4] |
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|
GnRH deficiency results from impairment of migration of the hormonal neurons to the hypothalamus in the embryological development.[5] |
| SOX 10 |
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| SEMA3A |
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| IL17RD |
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| FEZF1 |
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| Idiopathic hypogonadotrophic hypogonadism (IHH) (Normal smelling sensation - normosmia) | KISS1R |
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| KISS1 |
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| GNRHR |
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| GNRH1 |
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| TAC3 |
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| Mixed anosmic and nosmic IHH | FGFR1 |
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| FGF8[12] |
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| PROK2
PROKR2 |
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References
- ↑ Kumar P, Kumar N, Thakur DS, Patidar A (2010). "Male hypogonadism: Symptoms and treatment". J Adv Pharm Technol Res. 1 (3): 297–301. doi:10.4103/0110-5558.72420. PMC 3255409. PMID 22247861.
- ↑ Spratt DI, Carr DB, Merriam GR, Scully RE, Rao PN, Crowley WF (1987). "The spectrum of abnormal patterns of gonadotropin-releasing hormone secretion in men with idiopathic hypogonadotropic hypogonadism: clinical and laboratory correlations". J Clin Endocrinol Metab. 64 (2): 283–91. doi:10.1210/jcem-64-2-283. PMID 3098771.
- ↑ Boehm U, Bouloux PM, Dattani MT, de Roux N, Dodé C, Dunkel L; et al. (2015). "Expert consensus document: European Consensus Statement on congenital hypogonadotropic hypogonadism--pathogenesis, diagnosis and treatment". Nat Rev Endocrinol. 11 (9): 547–64. doi:10.1038/nrendo.2015.112. PMID 26194704.
- ↑ Franco B, Guioli S, Pragliola A, Incerti B, Bardoni B, Tonlorenzi R; et al. (1991). "A gene deleted in Kallmann's syndrome shares homology with neural cell adhesion and axonal path-finding molecules". Nature. 353 (6344): 529–36. doi:10.1038/353529a0. PMID 1922361.
- ↑ Schwanzel-Fukuda M, Bick D, Pfaff DW (1989). "Luteinizing hormone-releasing hormone (LHRH)-expressing cells do not migrate normally in an inherited hypogonadal (Kallmann) syndrome". Brain Res Mol Brain Res. 6 (4): 311–26. PMID 2687610.
- ↑ Pingault V, Bodereau V, Baral V, Marcos S, Watanabe Y, Chaoui A; et al. (2013). "Loss-of-function mutations in SOX10 cause Kallmann syndrome with deafness". Am J Hum Genet. 92 (5): 707–24. doi:10.1016/j.ajhg.2013.03.024. PMC 3644631. PMID 23643381.
- ↑ Cariboni A, Davidson K, Rakic S, Maggi R, Parnavelas JG, Ruhrberg C (2011). "Defective gonadotropin-releasing hormone neuron migration in mice lacking SEMA3A signalling through NRP1 and NRP2: implications for the aetiology of hypogonadotropic hypogonadism". Hum Mol Genet. 20 (2): 336–44. doi:10.1093/hmg/ddq468. PMID 21059704.
- ↑ Teles MG, Bianco SD, Brito VN, Trarbach EB, Kuohung W, Xu S; et al. (2008). "A GPR54-activating mutation in a patient with central precocious puberty". N Engl J Med. 358 (7): 709–15. doi:10.1056/NEJMoa073443. PMC 2859966. PMID 18272894.
- ↑ Bouligand J, Ghervan C, Tello JA, Brailly-Tabard S, Salenave S, Chanson P; et al. (2009). "Isolated familial hypogonadotropic hypogonadism and a GNRH1 mutation". N Engl J Med. 360 (26): 2742–8. doi:10.1056/NEJMoa0900136. PMID 19535795.
- ↑ Gianetti E, Tusset C, Noel SD, Au MG, Dwyer AA, Hughes VA; et al. (2010). "TAC3/TACR3 mutations reveal preferential activation of gonadotropin-releasing hormone release by neurokinin B in neonatal life followed by reversal in adulthood". J Clin Endocrinol Metab. 95 (6): 2857–67. doi:10.1210/jc.2009-2320. PMC 2902066. PMID 20332248.
- ↑ González-Martínez D, Kim SH, Hu Y, Guimond S, Schofield J, Winyard P; et al. (2004). "Anosmin-1 modulates fibroblast growth factor receptor 1 signaling in human gonadotropin-releasing hormone olfactory neuroblasts through a heparan sulfate-dependent mechanism". J Neurosci. 24 (46): 10384–92. doi:10.1523/JNEUROSCI.3400-04.2004. PMID 15548653.
- ↑ Falardeau J, Chung WC, Beenken A, Raivio T, Plummer L, Sidis Y; et al. (2008). "Decreased FGF8 signaling causes deficiency of gonadotropin-releasing hormone in humans and mice". J Clin Invest. 118 (8): 2822–31. doi:10.1172/JCI34538. PMC 2441855. PMID 18596921.
- ↑ Cole LW, Sidis Y, Zhang C, Quinton R, Plummer L, Pignatelli D; et al. (2008). "Mutations in prokineticin 2 and prokineticin receptor 2 genes in human gonadotrophin-releasing hormone deficiency: molecular genetics and clinical spectrum". J Clin Endocrinol Metab. 93 (9): 3551–9. doi:10.1210/jc.2007-2654. PMC 2567850. PMID 18559922.