Regulation of Adrenal Function 1

Question 1

Zones of Adrenal Cortex

Answer 1

ZG: Mineral (Aldosterone)

ZF: Gluco (Cortisol)

ZR: Androgens (DHEA/Androstenedione)

Question 2

ACTH derivative? Similar hormones?

What is the result of ACTH overproduction?

Answer 2

POMC: Also makes B-endorphins + MSH

Low-affinity binding to MC1H receptors leading to Skin darkening

Question 3

Main stimulators of ACTH

Answer 3

• DEC Cortisol
• Sleep-wake transition
• Stress: Hypoglycemia; Surgery + Trauma

Question 4

Immediate effects of ACTH -> INC cAMP in adrenal cortex

Answer 4

• INC Chol esterase,
• INC Chol transport
• INC Chol binding p450;
• INC pregnenolone,
• INC StAR Protein

Question 5

Significance of StAR Protein?

Answer 5

• Essential CYP11A1 transporter regulator of free cholesterol into Mt
• Inactivating StAR mutation -> INC fre Cholesterol -> Cytoplasmic accumulation + No cortisol formation (ACTH activation) –> Lipoid adrenal Hyperplasia

Question 6

What two enzymes are common to both cortisol + aldosterone synthesis? What do they do?

Which other two enzymes are needed for aldosterone + Cortisol?

Answer 6

CYP11A1/SCC: Removal of side chain (Cholesterol -> Pregnenolone

3B-HSD: Pregnenolone -> Progesterone

21-hydroxylase + 11 hydroxylase

Question 7

cholesterol desmolase RATE LIMITING enzyme in mitochondria? Function?

Answer 7

CYP11A1/SCC - Side chain cleavage

Question 8

21 B-hydroxylase deficiency

• Path
• Consequences

Answer 8

• Path: Enzyme important in the production of cortisol, DOC, + Aldosterone deficient –> Overproduced DHEA
• Con: Salt wasting, Hypoglycemia, + Virilization

Question 9

11 B-hydroxylase deficiency

• Path
• Consequences

Answer 9

• Path: Def in Enzymes in ONLY Cortisol + Aldosterone (INC DOC); INC DHEA
• Con: DOC -> Inhibit Ang II; INC Na+, Fluid retention, hypoglycemia, virilization

Question 10

17 hydroxylase deficiency

• Path
• Consequences

Answer 10

• Path: Enzyme Def in Cortisol + Androgen synthesis; INC DOC

- Con: HTN (Loss of Ang II)

Question 11

What hours are cortisol secretions highest

Answer 11

8a-12p

Question 12

Cellular + Molecular Mechanism of Action of Glucocorticoids

Answer 12

• Cortisol (S) binds IC Glucocorticoid Receptor (GR)
• Release of Neg regulators (HSP/IP)
• Translocation into nucleus + binding of Response elements (GRE) on targeted genes

Question 13

Anti-inflammatory mechanisms of glucocorticoids

Answer 13

Before response: Stabilization of lysosomal membrane

After: Induce synthesis of lipocortin; inhibit IL-2; Inhibit Histamine + Serotonin; DEC capillary perm; DEC WBCs

Question 14

Actions of Glucocorticoids

Answer 14

• INC Protein Catabolism
• DEC Insulin sensitivity
• INC Lipolysis: Glycerol -> liver gluconeogenesis
• Promote glycogenolysis in the liver
• Vasoconstrictor effect of NE in arterioles
• INC expression of alpha + Beta Receptors

Question 15

Glucocorticoid Use

Answer 15

• Immunosuppressants in Organ rejection, allergic rxn
• Anti-emetics in Chemo
• Induce lung surfactant before birth

Question 16

Addisons Disease

• Path
• Complication

Answer 16

• Path: Autoimmune destruction of Adrenals -> DEC GCC, Androgens, + Mineralocorticoids (Primary adrenal insufficiency)
• Comp: Addisonian crisis -> Medical emergency; S/S: Weakness, confusion, N/V, Hypotension, shock, seizure/coma

Question 17

Secondary Adrenal Insufficiency:

• Path
• S/S

Answer 17

• Path: Hypothalamic-pituitary failure; often drug induced from SYNTHETIC (EXOGENOUS) STEROIDS
• S/S: similar to Addison, BUT NO hyperpigmentation, Hyperkalemia, metabolic acidosis