Lecture 6 Flashcards
(46 cards)
What are mineralocorticoids?
steroid hormones that regulate sodium/water balence
What is the primary mineralocorticoids?
aldosterone
- other steroid hormones can have mineralocorticoid actions
ex: 11-deoxycorticosterone (precursor of aldosterone) has mineralocorticoid action
Where is MR expression high?
distal tubule in kidney
colon
salivary duct
sweat ducts
In the kidney what does aldosterone stimulate?
sodium and water reabsorption in kidney; increases potassium secretion
- aldosterone increases transepithelial Na transport in the distal tubule and collecting duct
- also promotes potassium excretion in collecting duct
-increases in extracellular fluid K+ concentration stimulate aldosterone release
–>increased extracellular fluid volume and blood pressure ( sodium in extracellular space retains water)
What happens when there is a decrease in blood pressure?
- renin release from the kidney (juxtaglomerular apparatus)
- renin cleaves angiotensinogen to angiotensin 1
- angiotensin converting enzyme converts to angiotensin 2
- angiotensin 2 is a vasoconstrictor and stimulates aldosterone
Does increased cortisol lead to increased angiotensinogen?
yes
Aldosterone vs. AVP
Aldosterone-primary regulator of extracellular volume
AVP-primary regulator of free water balance
What does AVP do?
- stimulates distal nephron water permeability-increased water retention
- decreases plasma osmolarity which secondarily affects sodium concentration in the blood
What does MR bind with high affinity to?
glucocorticoids and mineralocorticoids
Is there more glucocorticoids or mineralocorticoids?
glucocorticoids are 100-1000 fold higher than mineralocorticoids- but 95% is bound to CBG
Does aldosterone have a specific binding protein?
no
What happens does the conversion of cortisol to cortisone do? What does this conversion?
- inactivates glucocorticoids
- 11 B-HSD Type 2
What happens if 11BHSD2 is inhibited?
excess MR activation
What does local production of cortisol by 11B-HSD1 have potential pathogenic role in?
Diabetes type 2
cortisone
inactive
What is DHEA/S made in the zona reticularis?
androstendione
-precursor for the more potent androgen testosterone and for estrogens-converted in reproductive tissues
-weak androgen-due to its low binding affinity for androgen receptors
Where do 50% of total androgen precursors in adult male prostate come from?
adrenal
-declines with age-peaks between 20-30
How doe DHEA/S affect women?
-increases libido in women; primary source of androgen and estrogen in postmenopausal women
What is the first step in the steroid hormone synthesis? What are the steps leading to this step ?
conversion of cholesterol to pregnenolone
- LDL or HDL imports cholesterol into the cell
- Free cholesterol is esterified by: cholesterol ester hydrolyase
- cholesterol ester hydrolyase stimulated by ACTH - Steroidogenic regulatory protein (StAR) transfers cholesterol from outer mitochondria to inner mitochondria
What is the rate limiting step in steroid biosynthesis? What is regulated by?
StAR transfer of cholesterol into inner mito
-regulated by ACTH
What is 21 hydroxylase deficiency?
1. Most common: 21 hydroxylase deficiency-results in excess DHEA, no mineralocorticoids or glucocorticoids -virilization, ambiguous genitalia at birth, sodium loss Clinical presentation: Hypotension Hyperkalemia High plasma renin Musculation High ACTH
What zone is the enzyme cholesterol side chain cleavage in? what is the gene?
all
11A1
What zone is the enzyme 21 alpha-hydroxlase in? what is the gene?
fasciculata and glomerulosa
21A2
What zone is the enzyme 11-hyroxylase in? what is the gene?
fasciculata=11B1
Glomerulosa=11B2
