Steroid Hormones and Vitamin D Flashcards
1
Q
Synthesis of steroid hormones
A
-Involves shortening the hydrocarbon chain of cholesterol and hydroxylating the steroid nucleus
2
Q
Rate limiting step in steroid hormone synthesis
A
- Conversion of cholesterol to 21C pregnenolone
- Catalyzed by the cholesterol side chain cleavage enzyme (desmolase, CPY11A, P450SCC)
- Requires NADPH and O2
3
Q
CPY11A
A
- Cytochrome p450 oxidase in inner mitochondrial membrane
- Coverts cholesterol to pregnenolone
- Requiers NADPH and O2
4
Q
StAR
A
- Steroidogenic acute regulatory protein
- Moves cholesterol from the outer mitochondrial matrix to the inner mitochondrial matrix
5
Q
Congenital adrenal hyperplasias
A
-Defect at any step in steroid hormone synthesis
6
Q
3-B-Hydroxysteroid dehydrogenase deficiency
A
- Prevents conversion from pregnenolone to progesterone
- Reduction in all steroid hormones (glucocorticoids, mineralcorticoids,active androgens, estrogens)
- Salt excretion in urine
- Female like genitalia
7
Q
17-alpha Hydroxylase Deficiency
A
- Prevents conversion from progesterone to 17-alpha hydroxyprogesterone
- Virtually no sex hormones or cortisol
- Increased production of mineralcorticoids
- Fluid and sodium retention leads to hypertension
- Female like genitalia
8
Q
21-alpha Hydroxylase Deficiency
A
- Prevents conversion from progesterone to 11 deoxycorticosterone and prevents conversion from 17-alpha hydroxyprogesterone to 11 deoxycortisol
- Most common of congenital adrenal hyperplasias
- Mineralcorticoids and glucocorticoids virtually absent
- Overproduction of androgens
9
Q
11-B1 Hydroxylase Deficiency
A
- Prevents conversion of 11-deoxycorticosterone to corticosterone and conversion of 11-deoxycortisol to cortisol
- Decrease in serum cortisol, aldosterone, and corticosterone
- Increased production of 11-deoxycortiosterone causes fluid retention (suppresses renin-angiotensin system)
- Overproduction of androgens
10
Q
Location of cortisol production
A
-Middle layer, zona fasiculata of adrenal cortex
11
Q
Cortisol synthesis
A
- Binds G protein coupled receptor
- Increased cAMP
- Activated PKA
- PKA activates the lipase that converts cholesterol ester to cholesterol and the StAR protein
- Cholesterol moves to IMM and converted to pregnenolone
- Pregnenolone returned to the cytosol and converted to progesterone
- Progesterone converted to 11-deoxycortisol (CPY17 & CPY21)
- 11-deoxycortisol returned to IMM and converted to cortisol by CPY11B1
12
Q
Aldosterone physiological functions
A
- Produced in zona glomerulosa, outer layer of adrenal cortex
- Production stimulated by decrease in plasma Na/K ratio and by angiotensin II
- Angiotensin II binds a G coupled surface receptor and acts through the phosphatidylinositol 4,5 bisphosphate pathway
- Works primarily on kidney tubules to enhance Na and water uptake and K efflux
- Increases blood pressure
- ACE inhibitors used to treat renin-dependent hypertension
13
Q
Androgens production
A
- Produced by zona reticularis (inner layer) and middle layer
- Adrenal androgens (androsterone and androstenedione) converted to testosterone and estrogen in peripheral tissues
- Estrogen produced from androstenedione and then testosterone using aromatase
14
Q
Action of steroid hormone at molecular level
A
- Bind receptors inside of cell that enters the nucleus
- Dimerization and coactivator proteins
- Binds a hormone response element
- HRE is in the promoter or enhancer element for genes that are responsive to steroid hormones
- Binding of ligand exposes a DNA binding domain that allows the complex to associate with DNA through a zinc finger motif
15
Q
Metabolism and excretion of steroid hormones
A
- Conjugated with glucuronic acid or sulfate to make them more water soluble (in liver)
- Some secreted into bile and feces, the rest in the urine
- NO protein carriers needed because they are water soluble
