5_Adrenal Flashcards
What are the effects of epinephrine?
primarily fight-or-flight
What are the effects of norepinephrine
strong vasoconstrictor to increase BP
What is the outermost layer and thinnest of the adrenal cortex?
zona glomerulosa
What is the middle and thickest layer of the adrenal cortex?
zona fasciculate
What is the innermost layer of the adrenal cortex?
zona reticularis
What hormones does the zona fasciculate release?
glucocorticoids
What hormones does the zona reticularis secrete?
adrenal androgens (DHEA and androstenedione)
What hormones does the zona glomerulosa release?
aldosterone
How is the zona glomerulosa regulated?
by AngII and K+
How is the zona fasciculate regulated?
ACTH
How is the zona reticularis regulated?
ACTH
What is a pheochromocytoma?
a medullary tumor that causes a sporadic secretion in response to palpation or anesthetics
What are the clincal consequences of a pheochromocytoma?
postural hypotension: prolonged increase in catecholamines downregulates GPCRs to cause a reduction in sympathetic tone
Describe the cellular make-up of the adrenal medulla.
post-ganglionic neurons (“chromaffin cells”) that secrete the catecholamines epinephrine and norepinephrine
Where are the chromaffin cells derived?
they are sympathoadrenal & derived from the neural crest
How are norepi and epi synthesized?
from tyrosine - l-dopa - dopamine - norepi - epi
Where is norepi primarily converted to epi?
in the adrenal gland
What is the reaction catalyzed by cholesterol desmolase?
cholesterol P450 side-chain-cleavage to yield pregnenolone
What is the RLS in steroidogenesis?
cholesterol desmolase P450 scc
What is required for CD450scc activation?
ACTH
How does ACTH activate CD450scc?
activates G-alpha-S pathway
What factors increase aldosterone synthesis?
AngII and K+
What factors decrease aldosterone synthesis?
increased Na (mild decrease in synthesis)
Where is renin secreted?
JG cells
Upon response to what factors is renin secreted?
decreased pressure, beta-1 stimulation, decreased NaCl
What are the effects of AngII?
1) thirst, 2) vasoconstriction, 3) aldosterone
What are the major & minor mineralocorticoids?
major: aldosterone; minor: deoxycorticosterone, cortisone
What are the synthetic mineralocorticoids?
agonist: 9-alpha-fludrocortisone; antagonist: spironolactone
For what diseases is 9-alpha-fludrocortisone used?
addisons
For what disease is spironolactone used?
CHF
How does spironolactone work?
prevents aldosterone-MR binding
How does amiloride work?
prevents formation of new Na channels
Where do the mineralocorticoids act (cell types)?
principle cells of CT, also DT and CD
What are the effects of the mineralocorticoids?
Na/H2O reabsorption and K secretion
What are the symptoms of hypokalemia?
muscle weakness and paralysis
What are the symptoms of hyperkalemia?
cardiac toxicity
What are the axes of the RFC?
sodium intake (x normal) vs. BP
What is aldosterone effect?
short-term aldosterone effects due to pressure di-/natriuresis after 24-48h
Where does aldosterone bind its receptor?
binds MR in cytoplasm
What is aldosterone’s receptor?
the mineralocorticoid receptor (a nuclear receptor)
How does the aldosterone-MR complex initiate cell changes?
1) MR-Ald releases HSP, 2) MR-Ald translocates to nucleus, 3) MR-Ald is phosphorylated, 4) MR-Ald forms a homodimer, 5) 2 MR-Ald binds to GRE in promoter regions
What are aldosterone’s effects on its target cells?
1) increases Na/K ATPase, 2) increases Enac (epithelial sodium channel), 3) increases mitochondria
What are the major/minor glucocorticoids?
major: cortisol (hydrocortisone); minor: corticosterone
What are the synthetic glucocorticoids?
1) cortisone, 2) prednisone, 3) dexamethasone
What are the 5 stages of inflammation?
1) release of pro-inflammatory mediators, 2) erythema, 3) increased capillary permeability, clotting, and non-pitting edema/swelling, 4) leukocyte infiltration, 5) tissue remodeling and healing
How do glucocorticoids oppose inflammation?
1) stabilizes lysosomal membranes, 2) decreases capillary permeability (by inhibiting COX2), 3) opposis leukocyte infiltration (chemotaxis via stopping leukotrienes), 4) suppresses T-lymphocytes, 5) decreases IL-1 (decreases fever)
What are the immune effects of glucocorticoids?
1) decreased allergy inflammatory response, 2) decreased eosinophils & lymphocytes, 3) increased lymphoid atrophy, 4) increased RBCs
What systems do the glucocorticoids affect?
muscle, liver, adipose, immune/inflammation
What are the glucocorticoid effects on muscle?
muscle wasting & t2dm via inhibiting GLUT4 translocation
What are the glucocorticoid effects on the liver?
increases glycogen, increases gluconeogenesis, increases insulin
What are the effects of glucocorticoids in adipose?
lipolysis, but insulin overpowers to cause lipogenesis
What enzyme converts cortisone to cortisol?
11-beta-HSD
What is a Type 1 receptor?
the MR
What is a type 2 receptor?
GR
Where and when is CRF released?
by PVN of hypothalamus under stress
What is the function of PC1?
splits POMC to ACTH and beta-lipotropin; in the anterior pituitary
What is the function of PC2?
splits PC1 products to MSH and inactivated ACTH; in the hypothalamus
What is MSH?
melanocyte stimulating hormone
What are the effects of MSH?
1) melanin formation and dispersion, 2) decreased food intake/water consumption, 3) increased blood flow to brain, 4) increased tissue respiration
From what pre-prohormone is ACTH derived?
POMC (proopiomelanocortin)
What are the feedback loops in CRF/ACTH/cortisol?
cortisol inhibits CRF and ACTH (short and long loops)
What percentage of the adrenal gland is the medulla?
10-20%
Where is the type 1 (MR) receptor present?
in the kidney tubule
What are the relative affinities of corticosterone and aldosterone for the type 1 (MR) receptor?
they are equal
What are the relative affinities of corticosterone and aldosterone for the type 2 (GR) receptor?
corticosterone has greater affinity
Why does cortisone have aldosterone effects at high concentrations?
if 11-beta-HSD is overwhelmed, cortisol is not converted to cortisone and cortisol can trigger aldosterone-like (HTN) effects
What enzymes must be present to synthesize aldosterone?
aldosterone synthase
What enzymes must be present to synthesize the glucocorticoids?
17-alpha, but NOT 17,20
What enzymes must be present to synthesize the adrenal androgens?
17-alpha, AND 17,20
What are the adrenal androgens and what role do they play?
weak androgens that play large role in fetal development
What do adrenal androgens cause in males?
precocious puberty and stunted growth
What do adrenal androgens cause in females?
masculinization
What causes primary aldosteronism?
zona glomerulosa tumor
What is the treatment for primary aldosteronism?
surgery then aldosterone replacement
What is another term for addison’s disease?
hypoadrenalism
What is another term for cushing’s disease?
hyperadrenalism
What are the causes of Cushing’s?
1) too much CRF: dysfuntional HT; 2) too much ACTH: anterior pituitary adenoma; actopic ACTH tumor; 3) too much cortisol: cortical adenoma; glucocorticoid therapy
What are the treatments for Cushings?
1) surgery, 2) block steroidogenesis with ketoconazole, 3) block ACTH secretion (serotonin antagonists and GABA-TA inhibitors)
What are the symptoms of Cushings?
buffalo torso (upper body fat), moon face, acne, hirsuitism, hyperglycemia
