Endocrine 4 - Adrenal Roids Flashcards
What are the four histologic zones of the adrenal gland and what do the cells in each zone make?
From superficial to deep: Zona Glomerulosa --> aldosterone Zona Fasciculata --> cortisol Zona Reticularis --> androgens Medulla --> catecholamines
What is a mineralocorticoid?
Cholesterol-derived hormone that influences salt/water balance. Aldosterone is the big boy.
What is a glucocorticoid?
Cholesterol-derived hormone that influences glucose metabolism. Cortisol is the major one in the plasma.
In aldosterone synthesis, cholesterol is first converted to _________ by the enzyme _______. However, the rate limiting step is prior to this reaction. What is the rate limiting step?
cholesterol –> pregnenolone by CYP1A1
Before that, though, StAR (steroid acute regulatory protein) brings cholesterol from the plasma membrane into the mitochondria, and that is the rate-limiting step.
Describe the two forms in which cortisol can be found in the plasma.
The large majority of cortisol is bound to transcortin (a protein), and a small amount is free in the plasma. The free cortisol is what actually does stuff, and its in equilibrium with the transcortin-bound cortisol.
When should a clinician measure cortisol levels? Explain.
In the morning shortly after the patient wakes up, cuz that’s when they peak.
What is the cellular location of the cortisol receptor? What happens after cortisol binds the receptor?
In the cytoplasm. Cortisol binds, displaces Hsp90 (a thing that prevents nuclear binding), then transcription happens after that.
Which tissues bind cortisol? What are the effects of cortisol on each tissue?
Liver - cortisol stimulates gluconeogenesis.
Skeletal muscle - cortisol inhibits GLUT-4 glucose uptake.
Adipose tissue - cortisol (1) stimulates lipolysis, (2) inhibits lipogenesis, and (3) inhibits GLUT-4 glucose uptake.
Does gluconeogenic enzyme activity increase after administration of cortisol?
Yeah
Why do people with Cushing’s have muscle weakness? What hormone counteracts this effect?
Cortisol promotes proteolysis, insulin counteracts it.
How does cortisol effect catecholamine (epi, norepi) and glucagon signaling?
It enhances signaling by increasing (1) the amount of receptors, (2) adenylate cyclase, (3) cAMP, and (4) protein kinase A - which are all involved in the signaling process.
What are the five effects of glucocorticoids on the immune system?
- Inhibits production of inflammatory cytokines.
- Inhibits T cell proliferation.
- Promotes T cell apoptosis.
- Inhibits leukocyte chemotaxis.
- Inhibits prostaglandin production.
How exactly do glucocorticoids inhibit prostaglandin production?
Glucocorticoids promote synthesis of Annexin A1 aka Lipocortin, which inhibits phospholipase A2, the enzyme that acts on plasma membrane phospholipids to make arachidonic acid (precursor for prostaglandin).
Does the hypothalamus integrate a bunch of info, then release CRH if it wants to?
Yeah
Describe the hypothalamic-pituitary-adrenal axis and its feedback mechanism as it relates to cortisol.
Long feedback loop.
Also note that ADH acts synergistically with CRH to promote ACTH release, but cortisol doesn’t feed back to inhibit ADH.
What receptor binds ACTH? What second messengers are used?
7TM receptor. G protein –> cAMP –> protein kinase A –> decrease in glycogen synthesis, increase in cholesterol synthesis
When does Addison’s disease cause hyperpigmentation of the skin?
When there is a primary defect in the adrenal glands (usually from autoimmune destruction of the gland). There is no cortisol to feedback to the pituitary –> tons of ACTH. alpha-MSH is also cleaved from POMC, the precursor of ACTH, so more ACTH = more MSH.
When does Addison’s disease not cause skin hyperpigmentation?
When there is a defect in the hypothalamus or pituitary –> low ACTH levels cause hypocorticism, and low ACTH means low MSH.
What is the difference between Cushing’s disease and Cushing’s syndrome? Which one causes hyperpigmentation and why?
Cushing’s disease is when there is a tumor of the hypothalamus or pituitary –> lots of ACTH, lots of MSH (pigmented).
Cushing’s syndrome (without Cushing’s disease) is hypercorticism from a defect in the adrenals, not pigmented cuz ACTH levels are low.
Name five clinical features of Cushing’s diasease.
- Moon face
- Buffalo hump
- Abdominal striae
- Poor wound healing
- Muscle weakness
Describe the exact action of aldosterone.
Acts on distal tubule and CD cells, upregulates the Na+/K+ ATPase to pump sodium into the cell and potassium into the tubule lumen (gain of sodium, loss of potassium) –> increased BP and volume.
What are the four stimulants of the renin-angiotensin-aldosterone system?
- Decreased blood pressure
- Reduced blood volume
- Reduced osmolarity
- Elevated plasma K+
Which two adrenal cortex hormones exhibit receptor cross-reacivity? Describe the mechanism that protects against inadvertent cross-stimulation.
Cortisol and aldosterone can activate each other’s receptors. There is a lot more cortisol in the blood than there is aldosterone, so in order for aldosterone receptors to not go nuts over cortisol, the aldosterone receptors express 11beta-hydroxysteroid dehydrogenase, which converts cortisol to cortisone, an inactive metabolite.
Which amino acid are the catecholamines derived from? How does cortisol control their synthesis?
Derived from tyrosine. Cortisol regulates the expression of PNMT, a methyl transferase that converts norepinephrine to epinephrine.
What are the two major enzymes that degrade the catecholamines? What is the end product?
MAO and COMT. End product is vanillylmandelic acid, ends up in the urine.
One action that cortisol does NOT have is to:
a) stimulate gluconeogenesis in the liver
b) increase the sensitivities of tissues to epinephrine
c) stimulate skeletal muscle proteolysis between meals
d) promote wound healing
e) inhibit ACTH production
d) promote wound healing
- it suppresses the immune system
ACTH acts on the adrenal cortex through what second messenger systems?
a) cGMP and PIP3/diacylglycerol
b) tyrosine kinases and Ca+2
c) Ca+2 and PIP3/diacylglycerol
d) cAMP
e) cGMP
d) cAMP
Aldosterone acts in the kidney to:
a) reduce K+ reabsorption
b) stimulate Ca+2 reabsorption
c) stimulate K+ reabsorption
d) reduce Na+ reabsorption
e) stimulate Na+ reabsorption
e) stimulate Na+ reabsorption
