Physiology of Adrenal Cortex Flashcards
What are the zones of adrenal cortex?
Zona glomerulosa, fasciculata, reticularis
Major function of aldosterone
Increase Na absorption and K secretion to maintain fluid volume
Major function of glucocorticoids
provide sustained energy source. Enhance gluconeogenesis in liver, increase fatty acids, raise blood glucose level
Major function of catecholamines
rapid response to stress; fuel availability to increase CV function and performance
Major function of adrenal sex hormones
growth, developmental control in men and women
Describe globulin role in steroid binding.
High affinity reversible binding. Cs-binding globulin (CBP), aldosterone binding globuline, sex-steroid binding, progesterone binding
Describe the role of albumin in steroid binding
low affinity reversible binding
Describe the binding of cortisol
90% is bound to transcortin(majority) and albumin (minority), 10% is free, half life is 60 -90 minutes
Describe the binding of albumin
60% bound to transcortin, aldosterone binding globulin and albumin, 40% is free, half life is 20 minutes
What are the purposes of hormone protein binding?
Suppresses the biological activity of steroid hormones. Protect the hormone from structural alterations. Extend the half life time of hormones in the plasma. Provide an active hormone to the target tissue rapidly when needed.
___ is the source for synthesis of all steroids.
Cholesterol
What is the main cholesterol provider?
LDL.
_____ cholesterol is synthesized in the adrenal gland.
20%
Where are LDL receptors located in adrenal cortical cells?
plasma membrane
How is LDL transported into cells?
endocytosis. Internalization of LDL receptors within clathrin coated pits. Formation of endosomes and lysosomes. Cholesterol is released from receptors. LDL receptors are recycled.
How is cholesterol stored in adrenal cells?
cholesterol is esterified and stored in cytoplasmic vesicles until it is needed for the synthesis of corticosteroid hormone.
What is the mitochondrial rate limiting step in adrenal corticosteroid synthesis?
Cholesterol–> pregnenolone.
Key enzyme is CYP11A1.
How does neuroendocrine control steroidogenesis?
ACTH! stimulates CYP11A1, increase cholesterol uptake
What makes up 90% of all mineralcorticoid activity? Which is most potent
Aldosterone!
T or F Deoxycorticosteone is a glucocorticoid.
F–> mineralcorticoid
Describe the potency of deoxycorticosterone vs aldosterone
1/30
What is a synthetic potent aldosterone analogue that is slightly more potent than aldosterone?
9a-Fluorocortisol
What is the final step of aldosterone synthesis? What upregulates the enzyme?
corticosterone–> aldosterone
Enzyme is aldosterone synthase. Upregulated by Ang II
Mineralcorticoid synthesis occurs in the _____.
z. glomerulosa
Where are mineralcorticoid receptors found?
Kidneys, brain, lungs, heart, vascular tissues
Ligand binding properties of MRs
High receptor affinity for aldosterone. Non-specific activation by glucocorticoids. Cortisol: high affinity- high blood level- active ligand?
Cortisone- low receptor affinity, inactive ligand
Mineralcorticoid MOA for gene expression
- Aldosterone binds MR
- Translocated to nucleus
- Binding to promotor area of specific genes
- upregulation of gene expression of things like Na/K ATPase
What are the non-genomic effects of mineralcorticoids
via protein phosphorylation mediated cell signaling pathways
What glucocorticoids have mineralcorticoid activity?
corticosterone, cortisol, cortisone
What does 11B hydroxysteroid dehydrogenase do?
cortisol to cortisone
What 4 channels are regulated by aldosterone?
NaK ATPase, ENaC, Sgk1, ROMK
Sgk1 activates ____ to maintain _____.
Na/K ATPase, ENac, and ROMK; low intra Na and high intra K
Renal affects of mc on H
secretion; metabolic alkalosis; increase carbonic anhydrase
Renal affects of mc on HCO3
production; metabolic alkalosis; increase carbonic anhydrase
___ is the most potent GC and has __% of total gc activity
cortisol; 90%
Potency and percent gc activity of corticosterone
modest; 4%
What is the last step in cortisol synthesis?
11B- hydroxylase
Where to gc bind receptors?
cytoplasm
Genomic effects of GC
hormone receptor complex goes to nucleus, binds promoter regions, stimulates/repress gene expression, suppression via factors like NFkB
T or F the liver stimulates protein catabolism.
Falso. Other various organs but not liver.
What does GC do in adipose tissue?
promote lipolysis and enhance mobilization and oxidation of FA as an alternative energy source in starvation. Increase food uptake
High doses of oral cortisol can lead to ____.
Cushings. deposition of fat in chest and head, fat lump between shoulders, high BP, diabetes and bone loss
What cells are the main targets of cortisol in regard to immunity/inflammation
macs and t cell lymphocytes
What does GC do to collagen synthesis in the skin
decrease
What does GC do to Ca absoprtion in intestine? Kidney? blood? growth?
decrease all
Effect of GC on blood vessels
vasoconstriction, promote HTN, reduce blood clotting
Effect of GC on GI
stimulate GI function
Effect of GC on nervous system
suppress hypo-pit axis; increase appetite
What are the androgen precursors and androgens?
DHEA, androstenedione, testosterone
Effects of androgens on males and females
Males: weak
females: masculinization, adrenogenital syndrome
What are the female sex hormones?
progesterone and estrogens
What does adrenal medulla synthesize?
Epinephrine (80%), norepinephrine (20%)
Structure of hormones released by adrenal medulla
amino acid derivatives
Half life of hormones secreted by adrenal medulla
short, 2 min
What are the targets and functions of hormone secreted by adrenal medulla
heart, lungs, muscles, vessels, Immediate response to stress; Neural control
What are the effects of severe stress on hypothalamic pit. adrenal axis?
enlargement and hyperfunction leading to major health problems- heart disease, immunosuppression, digestive problems, sleep disorders, anxiety, depression
