Adrenal Physiology -Bi

Question 1

What are the cardiovascular effects of epinephrine?

Answer 1

beta 1 adrenergic: increase force and rate of myocardial contraction

alpha-1 adrenergic: vasoconstriction of vascular smooth mm.

beta-2 adrenergic: vasodilation of lungs and skeletal mm.

Question 2

What are the major differences in the CV effects of norepinephrine and epinephrine?

Answer 2

norepi does not act on beta 2 receptors (only alpha 1 and beta 1) ==> increase in both systolic and diastolic BP and total peripheral resistance (decrease HR and CO because of baroreceptor reflex)

epinephrine acts on beta 2 (and alpha 1 and beta 1) which leads to an increase in systolic BP, a decrease in diastolic BP, and a net reduction in total peripheral resistance (and an increase in HR and CO)

Question 3

What enzyme converts norepinephrine to epinephrine? What is this regulated by?

Answer 3

PNMT (only present in the adrenal medulla)

regulated by glucocorticoids

Question 4

What are the metabolic effects of Epi and norepi?

Answer 4

Direct: 
Induce glycogenolysis
Increase lipolysis
Increase liver glucose output
Non-shivering thermogenesis.

indirect:
Increase glucagon secretion
Inhibit insulin secretion

Question 5

What adrenal zone contains cells that express aldosterone synthase?

Answer 5

the zone glomerulosa –> produce aldosterone

Question 6

Which enzymes are necessary for the synthesis of glucocorticoids? Where are these found?

Answer 6

17 alpha-hydroxylase

the zona fasciculata

Question 7

Where are the cofactors for the synthesis of androgens located? What are the primary androgens produced here?

Answer 7

the cofactors for 17,20-lyase activity are in the zona reticularis

the hormones produced are dehyroepiandrosterone and androstenedione

Question 8

How does the half-life of cortisol and corticosterone compare to that of aldosterone? Why is that?

Answer 8

cortisol has a longer (90 min) (corticosterone is 60 min) half life compared to aldosterone because it is bound (mainly to costicosteroid-binging globulin and some albumin)

aldosterone is not bound (half life of 20 min)

Question 9

What happens to cortisol levels during pregnancy?

Answer 9

estrogen elevated the levels of CBG which causes total cortisol levels to increase but the free cortisol in plasma remains the normal.

Question 10

How are glucocorticoids metabolized?

Answer 10

by the liver (glucuronyl transferase) to tetrahydroglucuronide derivatives

Question 11

What effects do glucocorticoids have on ACTH? What type of rhythm is seen with both ACTH and GCs?

Answer 11

ACTH increase with circadian rhythm (elevated when a person is asleep) will cause an increase in GC production. Increase in GC will have a feedback effect on ACTH secretion–> inhibit ACTH

Question 12

What metabolic, vascular, immune system, and endocrine effects do glucocorticoids have?

Answer 12

metabolic: andi-insulin–> increase plasma glucose
vascular: enable vascular smooth mm to respond to catecholanimes (increase alpha receptors) and increase GFR (to maintain plasma volume)
immune: inhibit immune function (anti-inflammation)
endocrine: Brain: inhibit CRH and ACTH

Question 13

What is a major inhibitory factor for CRH and ACTH secretion?

Answer 13

circulating cortisol (at the level of the anterior pituitary and the hypothalamus)

regulates gene expression

Question 14

What happens to a person who is treated for a long time with glucocorticoids? How should they be taken off of this medication?

Answer 14

the exogenous GC will cause the CRH and ACTH levels to significantly decrease or not produce anything at all.

if the person is taken off the GC, it will take about 2-3 months for the ACTH to begin producing normally again and about 6 months for the GC to be produced normally.

SLOWLY remove the GC from the patient

Question 15

What is the starting point for ACTH synthesis?

Answer 15

POMC (proopiomelanocortin)

Question 16

What regulates the release of ACTH? What receptor is responsible for this?

Answer 16

CRH binds to CRH-1R –> activated Gs–> increase cAMP

Question 17

What byproduct is produced in the production of ACTH? What is this responsible for?

Answer 17

MSH (melanocyte-stimulating hormones) are the inactive byproduct which can change your skin pigmentation

Question 18

How does ACTH increase GCs? (what type of receptor? how does it work?)

Answer 18

ACTH increases GC synthesis and secretion by acting on Gs melanocortin receptors–> increase cAMP—> activate PKA –> activated CEH (cholesterol ester hydrolase) to increase cholesterol and its mitochondrial transport)

PKA also increases the gene expression of steroidogenic enzymes

ACTH increases its own receptor sensitivity

Question 19

What type of receptors are glucocorticoid receptors? How do they work? What are the alpha and beta variants of the receptor?

Answer 19

Nuclear receptors

GC enters the cell and interacts with GR (glucocorticoid receptor) to change GR conformation –> induce GR translocation and activate transcription of target genes

alpha is the responsive variant

GR beta is the dominant negative variant (in this non-active form when there is no GC present)

Question 20

What effect can long term Glucocorticoid treatment have on bones?

Answer 20

osteoporosis

increase in osteoclast activity and decrease in osteoblast activity

Question 21

What are the effects of aldosterone (mineralocorticoids)?

Answer 21

principal cells:

• increase ENaCs (epithelial Na+ channels on the apical side) and the Na+/K+ exchangers –> increase Na+ reabsorption
• induce serum and glucocorticoid regulared kinase (sgk) which causes the phosphorylation of ENaCs and an increase in their insertion into the membrane.
• increase K+ excretion due to the Na+/K+ exchange causing excess K+ into the cell–> inc. excretion

Intercalated cells:
-increase H+ ATPase proton pump (apical), and Cl-/HCO3- exchanger (basolateral) (nongenomic action)==> increase in H+ excretion and increase in pH (more basic)

Question 22

What is the major regulator of aldosterone release? How does this work? What are the other regulators of aldosterone release?

Answer 22

renin-angiotensin-aldosterone: renin is released from the kidney with decrease in ECF volume this causes the formation of angiotension I. ACE converts AG I –> AG II which causes an increase in SNS activity, increase in Na+ reabsorption and K+ excretion, increase in aldosterone secretion by the adrenals, vasoconstriction (increase in BP) and increase in ADH secretion from the pituitary ==> increase in water and salt retention and BP and circulating volume

other: K+ elevation-> open Ca2+ voltage gated channels–> increase Ca2+ –> increase aldosterone synthesis/release

Question 23

What inhibits renin secretion?

Answer 23

Atrial natriuretic peptide (ANP)

hypernatremia-induced increases in ANP cause a reduction in renin release and a decreased sensitivity of the zona glomerulosa to AG II stimulation. -> decreases aldosterone secretion and increases Na+ excretion

Question 24

What is the function of 21-hydroxylase? What will result due to a deficiency in this enzyme?

Answer 24

converts progesterone to 11-deoxycorticosterone (11-DOC) and converts 17alpha hydroxyprogesterone to 11-deoxycortisol

deficiency: dec cortisol and aldosterone–> loss of Na+, virilization (excess androgen production)

Question 25

What does 11beta-hydroxylase do? What will a deficiency in 11beta-hydroxylase cause?

Answer 25

-converts 11-deoxycorticosterone to corticosterone; 11-deoxycortisol to cortisol

excess 11-deoxycortisol and 11-deoxycorticosterone–> excess mineralocorticoid activity–> increase Na+ and water retention

Question 26

what is the function of 17 alpha hydroxylase? What will a deficiency in this enzyme lead to?

Answer 26

• converts pregnanolone to 17alpha-hydroxyprogesterone
• decreased cortisol and androgens and aldosterone
• (aldosterone is stimulated by AG II which is being decreased because the increase in 11-COD will elevate BP and will shut off the renin-angiotensin flow)