WBR0732

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Author [[PageAuthor::Yazan Daaboul, M.D. (Reviewed by Yazan Daaboul, M.D.)]]
Exam Type ExamType::USMLE Step 1
Main Category MainCategory::Physiology
Sub Category SubCategory::Endocrine
Prompt [[Prompt::A researcher is evaluating the role of the hypothalamic-pituitary-adrenal (HPA) axis in lifestyle stresses. She enrolls 120 healthy volunteers for the study and measures plasma concentrations of adrenal hormones during several activities. She notes that the main secretory product of the zona fasciculata of the adrenal gland may fluctuate depending on the type of activity performed. Which of the following molecular changes occurs in response to the increased plasma concentration of the compound secreted from the zona fasciculata?]]
Answer A AnswerA::Accumulation of cyclic AMP (cAMP)
Answer A Explanation [[AnswerAExp::Cortisol upregulates β-adrenergic receptors to increase the sensitivity of norepinephrine, and thus increase blood pressure. The mechanism by which cortisol or glucocorticoids achieve such permissive effect is by coupling the adrenergic receptors and the G-protein receptors to stimulate adenylate cyclase, which is sensitive to catecholamines, leading to cAMP accumulation.]]
Answer B AnswerB::Increase in plasma norepinephrine levels
Answer B Explanation AnswerBExp::Plasma levels of norepinephrine are unchanged with cortisol; but cortisol increases the sensitivity of norepinephrine and potentiates its effect by increasing the alpha-1 receptors in arterioles.
Answer C AnswerC::Decrease in plasma neutrophil count
Answer C Explanation AnswerCExp::Cortisol is associated with neutrophilia
Answer D AnswerD::Increase in plasma eosinophil count
Answer D Explanation AnswerDExp::Cortisol is associated with low eosinophil counts.
Answer E AnswerE::Increase in insulin sensitivity
Answer E Explanation AnswerEExp::Cortisol is associated with insulin resistance.
Right Answer RightAnswer::A
Explanation [[Explanation::Cortisol upregulates β-adrenergic receptors to increase the sensitivity to norepinephrine, and thus increase blood pressure. The mechanism by which cortisol or glucocorticoids achieve such permissive effect is by coupling the β-adrenergic receptors and the G-protein receptors to stimulate adenylate cyclase, which is sensitive to catecholamines, leading to cAMP accumulation. As such, it it believed that the target for cortisol to achieve its action is the β-adrenergic receptor. Following the administration of cortisol, the activity of β-adrenergic receptors increases to as much as 3 times its baseline value. Thyroid hormones are another example of permissive hormones that allow activity of other hormones that act through the cAMP pathway.

Educational Objective: Cortisol and glucocorticoids are permissive hormones that regulate the action of other hormones that act through cAMP pathway by targeting the adrenergic receptors.
References: Hadcock JR, Malbon CC. Regulation of beta-adrenergic receptors by "permissive" hormones: glucocorticoids increase steady-state levels of receptor mRNA. Proc Natl. Acad. Sci. USA. 1988;85:8415-8419.
First Aid 2014 page 313]]

Approved Approved::Yes
Keyword WBRKeyword::Cortisol, WBRKeyword::Norepinephrine, WBRKeyword::Blood, WBRKeyword::Pressure, WBRKeyword::Receptor, WBRKeyword::Adrenergic, WBRKeyword::Zona, WBRKeyword::Fasciculata
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