WBR0272

Author	[[PageAuthor::Serge Korjian, M.D., Gonzalo A. Romero, M.D. [1](Reviewed by Serge Korjian)]]
Exam Type	ExamType::USMLE Step 1
Main Category	MainCategory::Biochemistry, MainCategory::Physiology
Sub Category	SubCategory::Endocrine, SubCategory::General Principles
Prompt	[[Prompt::An experimental mouse model aims to assess the effect of a molecule found in excess in mice deprived of water. Following isolation of the molecule, it is administered by subcutaneous infusions to unrestrained, conscious mice that are provided with 5% dextrose solution to drink. Assessment after 30 minutes reveals significant retention of water and a decrease in serum sodium concentration. Which of the following is correct about this isolated molecule?]]
Answer A	AnswerA::It exerts its effects through nuclear receptors
Answer A Explanation	AnswerAExp::Both type 1 and type 2 ADH receptors are surface-bound. Thyroid hormones (T3/T4) exert their effects through nuclear receptors.
Answer B	AnswerB::It has receptors localized in the renal collecting tubules
Answer B Explanation	[[AnswerBExp::Type 2 ADH receptors are located at the basolateral aspect of the collecting tubules, particularly in the cortical and outer medullary collecting ducts. Once type 2 ADH receptors are activated, they stimulate downstream mediators via adenylate cyclase/cAMP that leads to aquaporin translocation to the luminal side.]]
Answer C	AnswerC::It has type 1 receptors that exert their action through cAMP
Answer C Explanation	AnswerCExp::Type 1 ADH receptors act via an IP3/DAG pathway
Answer D	AnswerD::It stimulates aquaporin translocation in the proximal tubules
Answer D Explanation	AnswerDExp::ADH acts only on the collecting tubules in the kidneys. It does not affect water reabsorption in the proximal tubules. Additionally, aquaporins are not found in the proximal tubules.
Answer E	AnswerE::It is a steroid hormone
Answer E Explanation	AnswerEExp::Vasopressin is not a steroid hormone. There are 5 main classes of steroid hormones: androgens, estrogens, progestins, mineralocorticoids, and glucocorticoids. Aldosterone is an example of a mineralocorticoid steroid hormone.
Right Answer	RightAnswer::B
Explanation	[[Explanation::The vignette describes the classical properties of vasopressin or antidiuretic hormone (ADH). Vasopressin has 2 main functions dictated by their receptors. Type 1 receptors or AVPR1 are found in most organs, particularly in the peripheral vasculature. Activation of AVPR1 results in vasoconstriction in states of reduced plasma volume. In contrast, type 2 receptors or AVPR2 are found on the basolateral membrane of the epithelial cells lining the renal collecting ducts. AVPR2 are activated in response to thirst, reduced plasma volume, and increased osmolarity to stimulate water reabsorption. Vasopressin binding to type 2 receptors activates a cAMP-mediated pathway that triggers the insertion of aquaporins (AQP2) on the luminal surface of the collecting tubules at the level of the kidney. Aquaporins are water channels that only allow water to be reabsorbed resulting in an increased urine concentration. Vasopressin is produced by magnocellular neurosecretory neurons in the supraoptic nucleus on the hypothalamus and are conducted via axonal projection to the posterior pituitary (hence the name neurohypophysis). This model replicates the syndrome of inappropriate ADH (SIADH) usually caused by pulmonay diseases, CNS disturbances, severe illnesses, and as an adverse effect of certain medications. The most prominent feature of SIADH is hyponatremia. Educational Objective: ADH/Vasopressin causes water reabsorption by binding to its type 2 ADH receptors located at the basolateral aspect of the collecting tubules. References: Verbalis JG. An experimental model of syndrome of inappropriate antidiuretic hormone secretion in the rat. Am J Physiol. 1984;247(4 Pt 1):E540-53. First Aid 2014 page 311]]
Approved	Approved::Yes
Keyword	WBRKeyword::ADH, WBRKeyword::Vasopressin, WBRKeyword::Renal, WBRKeyword::Kidneys, WBRKeyword::Water reabsorption, WBRKeyword::Sodium, WBRKeyword::SIADH, WBRKeyword::Urinary concentration, WBRKeyword::ADH receptor, WBRKeyword::Aquaporin
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