Adrenal Gland Physiology

Question 1

What are the two major parts of the adrenal gland and what does each secrete? What is the origin of each?

Answer 1

• inner medulla: 20% of tissue, secretes catecholamines (80% epinephrine and 20% norepinephrine), neuroectodermal origin (note that ACh stimulates the catecholamine secretion because the medulla is innervated by PREganglionic sympathetic neurons)
• outer cortex: 80% of tissue, secretes steroid the hormones mineralocorticoids (aldosterone), glucocorticoids (cortisol), and androgens, mesodermal origin
• (note that of the cortex, the zona fasiculata is by far the largest)

Question 2

What do the enzymes found in the adrenal cortex that convert cholesterol into steroid hormones require?

Answer 2

• cytochrome P-450
• O2
• NADPH

Question 3

Which enzymes are found in each layer of the adrenal cortex?

Answer 3

• all 3: cholesterol desmolase, 3beta-hydroxysteroid dehydrogenase
• glomerulosa and fasiculata: 21-hydroxylase, 11beta-hydroxylase
• fasiculata and reticularis: 17alpha-hydroxylase
• unique to glomerulosa: aldosterone synthase (AKA 18-hydroxylase)

Question 4

What is the rate-limiting step in corticosteroid hormone synthesis? What enzyme catalyzes this reaction? What regulates it?

Answer 4

• the 1st step: the conversion of cholesterol into pregnenolone
• this reaction is catalyzed by cholesterol desmolase
• cholesterol desmolase is stimulated by ACTH
• it is inhibited by ketoconazole

Question 5

How is aldosterone synthesized?

Answer 5

• made in the zona glomerulosa
• 1) cholesterol desmolase converts cholesterol into pregnenolone
• 2) 3beta-hydroxysteroid dehydrogenase converts pregnenolone into progesterone
• 3) 21-hydroxylase converts progesterone into 11-deoxycorticosterone
• 4) 11beta-hydroxylase converts 11-deoxycorticosterone into corticosterone
• 5) aldosterone synthase converts corticosterone into aldosterone
• aldosterone synthase is stimulated by angiotensin II; this is the major regulating factor (along with potassium levels) for aldosterone synthesis, NOT ACTH

Question 6

How is cortisol synthesized?

Answer 6

• made in the zona fasciculata
• 1) cholesterol desmolase converts cholesterol into pregnenolone
• 2) 17alpha-hydroxylase converts pregnenolone into 17-hydroxypregnenolone
• 3) 3beta-hydroxystreoid dehydrogenase converts 17-hydroxypregnenolone into 17-hydroxyprogesterone (note that 17alpha-hydroxylase can also form this precursor by acting on progesterone made in the glomerulosa)
• 4) 21-hydroxylase converts 17-hydroxyprogesterone into 11-deoxycortisol
• 5) 11beta-hydroxylase converts 11-deoxycortisol into cortisol

Question 7

What are the androgens that are made in the adrenal cortex? How are they synthesized?

Answer 7

• dehydroepiandrosterone (DHEA) and androstenedione are made in the zona reticularis
• 1) cholesterol desmolase converts cholesterol into pregnenolone
• 2) 17alpha-hydroxylase converts pregnenolone into 17-hydroxypregnenolone
• 3) cleavage of 17-hydroxypregnenolone forms DHEA
• 4) 3beta-hydroxysteroid dehydrogenase converts DHEA into androstenedione via
• androstenedione can be made into testosterone

Question 8

What happens to the androgens once they are secreted? Which enzymes are involved and where are they found?

Answer 8

• they are “activated” into stronger sex hormones in the periphery
• aromatase converts androstenedione into estrone (which can be made into estradiol), aromatase also converts testosterone into estradiol
• 5alpha-reducatse converts testosterone into dihydrotestosterone (DHT)
• (aromatase is found in adipose tissue and in the ovaries)
• (5alpha-reducatse is found in skin, testes, prostate, seminal vesicles, epidermis, liver, and ovaries)

Question 9

Which steroid hormone precursors have some activity?

Answer 9

• corticosterone (aldosterone’s direct precursor) is a weak mineralocorticoid and weak glucocorticoid
• 11-deoxycorticosterone AKA DOC (corticosterone’s direct precursor) is a weak mineralocorticoid
• (cortisol also actually has some weak mineralocorticoid activity)
• mineralocorticoids: aldosterone, 11-DOC, corticosterone, cortisol
• glucocorticoids: cortisol, corticosterone

Question 10

What are the 17-ketosteroids?

Answer 10

• 17-ketosteroids: dehydroepiandrosterone (DHEA) and androstenedione (these have a ketone group at C17)
• these are C19 steroids (having 19 Cs) vs. C21 steroids (which have a side chain containing 2 Cs at C17)

Question 11

What are the immediate, long-term, and chronic effects of pituitary ACTH on the adrenal cortex?

Answer 11

• (ACTH release is triggered by hypothalamic CRH)
• immediate: binds cholesterol to cytochrome P-450 and activates cholesterol desmolase
• long-term: increases transcription of cytochrome P-450 and adrenal ACTH receptors
• chronic: hypertrophy and hyperplasia of adrenal cortex

Question 12

What are the major effects of cortisol?

Answer 12

• (cortisol is a glucocorticoid)
• B.I.G. F.I.B.
• Blood pressure (upregulates alpha-1 receptors to increase responsiveness to catecholamines)
• Insulin resistance (diabetogenic)
• Gluconeogenesis (causes lipolysis and proteolysis to provide liver with fuel for gluconeogenesis)
• Fibroblast regulation (decreases fibroblast activity, weakens collagen)
• Immunosuppression and anti-Inflammatory (inhibits IL-2 production to suppress T-cells by inhibiting NF-kB, synthesizes lipocortin to inhibit phospholipase A2 from freeing arachidonic acid to prevent PG and LT synthesis)
• Bone formation inhibition (lowers osteoblastic activity and decreases synthesis of collagen)

Question 13

What are the major effects of aldosterone?

Answer 13

• (aldosterone is a mineralocorticoid)
• increases Na+ reabsorption and increases K+ secretion in renal principal cells (increases Na+-K+-ATPase pumps)
• increases H+ secretion in renal alpha-intercalated cells

Question 14

What type of hormone is each adrenal hormone?

Answer 14

• catecholamines (epinephrine and norepinephrine): amine hormones (derived from tyrosine)
• mineralocorticoids, glucocorticoids, androgens: steroid hormones