Lecture 19 - Adrenal Cortex Flashcards
Mineralocorticoids and Glucocorticoids can be generated from Pregnenolone and/or Progesterone. Which enzyme is specific to the glucocorticoid pathway and which is specific to the mineralocorticoid pathway?
Which enzymes are in the Mitochondria in these pathways?
Glucocorticoid –> 17alpha-hydroxylase
Mineralocorticoid –> Aldosterone synthase
Cholesterol side chain cleaving enzyme; 11beta-hydroxylase; Aldosterone Synthase
The reason the zona glomerulosa of the adrenal cortex produces only Aldosterone is because it lacks the enzyme ________.
The reason the zona fasciculata only produces ______ and androgens is because it lacks the enzyme _____ ______.
The reason the zona reticularis only produces androgens is because it lacks the enzyme ________.
17alpha-hydroxylase
Cortisol and androgens
Aldosterone Synthase
11beta-hydroxylase
90% of Cortisol is bound to Corticosteroid binding globulin (CBG) or ______ in the plasma. Its half-life is about 60-90mins.
Transcortin
50% of Aldosterone is bound with low affinity to CBG and ______ in plasma. Its half-life is about ____mins.
Albumin
20mins
Upon binding of glucocorticoid hormones to glucocorticoid receptors (GCR), _____ dissociates from GCR, allowing them to dimerize and bind receptor elements on DNA.
Mineralocorticoids and their receptors work in the same way.
HSP (heat shock protein)
How do renal tubule cells prevent cortisol from activating the mineralocorticoid receptor? Keep in mind cortisol has a high binding affinity for this receptor, so it would act in the same way aldosterone would, if allowed.
Renal tubule cells produce the enzyme 11beta-hydroxylsteroldehydrogenase (11beta-OHSD) that converts Cortisol to Cortisone, which has no affinity for the Mineralocorticoid receptor.
Which food inhibits 11beta-OHSD?
Licorice! So be on the lookout for a patient who likes candy and has high BP
In bone, Cortisol decreases ________ formation and decreases production of ______.
Osteoblast
IGF-1
Cortisol induces the production of ______, which inhibits phospholipase-A2 (so decreased conversion of Phosphatidyl choline to _____ ____ (the precursor to prostaglandins, thromboxane, and leukotrienes).
Lipocortin
Arachidonic Acid
ACTH stimulates mobilization and conversion of Cholesterol to pregnenolone at all steps in the pathway via its binding to the _______ 2 receptor –> activates AC –> increases cAMP –> activates PKA.
Melanocortin 2 receptor
______, a hormone produced by the heart in response to mechanical stretch from increased blood volume, inhibits the production and secretion of ______ in the zona glomerulosa.
ANP
Aldosterone
The most common cause of hypoadrenalism is abrupt cessation of exogenous _______ –> does not give time to restore endogenous production of ______.
Rarely, it can occur from Primary or Secondary adrenal insufficiency. Primary, caused by adrenal cortex destruction, is classified as ______ disease.
Glucocorticoids
ACTH
Addison’s disease
How will 21-hydroxylase deficiency present?
No production of Aldosterone OR Cortisol, so a resultant HIGH production of Androgens.
How do you differentiate clinically between 21-hydroxylase deficiency and 11beta-hydroxylase deficiency?
They will present the same except for BP and Natremia –> Both will be elevated in 11beta-hydroxylase deficiency bc DOC is still formed from conversion of Progesterone by 21-hydroxylase, and DOC has a strong mineralocorticoid effect. –> acts like aldosterone.
