Adrenal gland

Question 1

Adrenal cortex origin and secretion

Answer 1

• Derived from mesoderm

- Glucocorticoids (zona fasciculata), mineralcorticoids (zona glomerulosa), androgens (zona fasciculata/reticularis)

Question 2

Adrenal medulla origin and secretion

Answer 2

• Derived from neural crest
• Epinephrine, norepi, dopa, and dopamine
• Modified post-ganglionic sympathetic nerve cells

Question 3

Steroid hormone synthesis in adrenal cortex

Answer 3

• Precursor is cholesterol, LDL cholesterol, or de novo
• All enzymes are p450 oxidases except cytosolic 3B-hydroxysteroid dehydrogenase
• Rate limiting step is cholesterol to pregnenolone

Question 4

Aldosterone synthesis in zona glomerulosa

Answer 4

• Glomerulosa lacks 17alpha-hydroxylase but has aldosterone synthase
• No storage pool of aldosterone
• Reabsorption of Na and water in kidney, K secretion

Question 5

Cortisol and androgen synthesis in zona fasciculata/reticularis

Answer 5

• Have 17-alpha hydroxylase
• Most cortisol is bound to CBP or albumin, some free
• DHEA and Androstenedione are adrenal androgens, converted in peripheral tissues

Question 6

Cortisol mechanism of action

Answer 6

• Free cortisol enters target cell by diffusion
• Binds to cytoplasmic receptor
• Migrates to the nucleus
• Modulates gene transcription
• Inhibits expression of CRH receptor and ACTH and transcription of POMC gene

Question 7

11B-hydroxysteroid dehydrogenase type 2

Answer 7

• Converts cortisol to cortisone in the kidney
• Prevents sensing of cortisol as a mineralcorticoid
• Present in renal tubule cells

Question 8

Cortisol action

Answer 8

• Stimulates gluconeogenesis in liver, enhances protein breakdown, stimulates lipolysis, deposits fat centrally, decreases osteoblastic activity
• Inhibits cytokine and chemoattract molecule production, stabilizes lysosomal enzymes, contributes to vasoconstriction
• Decreases lymphocyte proliferation, inhibits hypersensitivity reactions
• Emotional instability
• Blocks glucose uptake except in the brain

Question 9

Cellular action of ACTH

Answer 9

• Released by pituitary
• Acts on melanocortin-2-receptor (G protein), activates AC, increases cAMP, activates PKA, increases activity of p450scc

Question 10

Cellular action of CRH

Answer 10

• Released by hypothal
• Acts on CRH receptor (G protein), activates AC, increases cAMP, activates PKA, intracellular Ca increases, ACTH released

Question 11

CRH

Answer 11

• Made in PVN of hypothalamus

- Acts on corticotroph cells

Question 12

ACTH

Answer 12

• Secreted by corticotroph cells of anterior pituitary

- Produced by post-translational processing of POMC

Question 13

Feedback inhibition of cortisol

Answer 13

• Negative feedback on ACTH and CRH
• Inhibits expression of POMC gene in anterior pit
• Decreases mRNA and peptide levels of CRH and prevents release of presynthesized CRH in the hypothal

Question 14

Post-translational processing of POMC

Answer 14

-Gives rise to ACTH and B-lipotropin

Question 15

Cushing’s syndrome

Answer 15

• Hyperadrenal function: excessive levels of cortisol for long periods of time
• Cushing’s disease: hypercortisolism secondary to excess production of ACTH from a pituitary gland adenoma
• Moon face, red face, upper body obesity, osteopenia, glucose intolerance, hypokalemia, hypertension

Question 16

Addison’s disease

Answer 16

• Hypoadrenal function
• Lack of aldosterone: hypotension, hypokalemia
• Lack of cortisol: hypoglycemia, weakness, weight loss
• Autoantibodies directed against adrenal cells containing 21 hydroxylase