Steroid Hormones Flashcards
What are the 5 classes of steroid hormones?
Glucocorticoids
Mineralocorticoids
Progesterone
Androgens
Estrogen
Which classes make up the corticosteroids?
1) Glucocorticoids
2) Mineralocorticoids
Which classes make up the sex steroids?
1) Progesterone
2) Androgens
3) Estrogen
What is Addison’s Disease
Failure to make Aldosterone/Cortisol
Low levels of corticosteroids
What is Cushing Syndrome
Excess overproduction of cortisol by the adrenal glands
Glucocorticoid function and example
Cortisol
- guide conversion of sugar, fat, protein to usable energy
- inhibit swelling and inflammation
- suppress immune responses
Mineralocorticoids function and example
Aldosterone
- regulate inorganic molecules to maintain H2O
- retention of Na+, excretion of K+ and H+
- retention of H2O leads to an increase in BV and BP
- release regulated by sensors in kidney
Androgens function and example
Testosterone
- development of sex organs
- converted to DHT in target tissues
- increases 30x in puberty
Progesterone
- prepares endometrium for implantation
- inhibits development of a new follicle
- mammary gland development
StAR Complex
Steroidogenic Acute Regulatory Protein
- Moves cholesterol into the mitochondria for synthesis
- Fatal if non-functional
When does cortisol synthesis occur
Occurs in the adrenal cortex following ACTH release by the pituitary gland
Which steps of cortisol synthesis occur in the mitochondria?
Cholesterol > Pregnenolone ….> Cortisol
Cortisol synthesis intermediates
Cholesterol > Pregnenolone > Progesterone > 17-⍺-Hydroxyprogesterone > 11-Deoxycortisol > Cortisol
Cortisol synthesis intermediates
20⍺-22 Desmolase
3ß-hydroxysteroid DH
17⍺-Hydroxylase
21⍺-Hydroxylase
11ß-Hydroxylase
Which step converts NADPH and O2 to NADP
11ß-Hydroxylase converting 11-Deoxycortisol to Cortisol
Where does Aldosterone synthesis occur?
Adrenal Cortex
Aldosterone synthesis intermediates
Cholesterol
Pregnenolone
Progesterone
11-deoxycortisone
Corticosterone
Aldosterone
Aldosterone synthesis enzymes
20⍺-22 Desmolase
3ß-hydroxysteroid DH
21⍺-Hydroxylase
11ß-Hydroxylase
Aldosterone Synthase
When is the ∆5 pathway of testosterone synthesis present as opposed to ∆4?
∆5 is dominant in humans, but ∆4 is still active (hamsters)
Testosterone ∆5 pathway intermediates
Cholesterol
Pregnenolone
17⍺-Hydroxypregnenolone
DHEA
Androstenedione
Testosterone
Estradiol (Estrone)
Testosterone ∆4 pathway intermediates
Cholesterol
Pregnenolone
Progesterone
17⍺-Hydroxyprogesterone
Androstenedione
Testosterone
Estradiol (Estrone)
Testosterone ∆5 pathway enzymes
20⍺-22 Amylase
17⍺-hydroxylase
17⍺-hydroxylase
3ß-hydroxysteroid DH
17ß-hydroxysteroid DH
Aromatase
Testosterone ∆4 pathway Enzymes
20⍺-22 Amylase
3ß-hydroxysteroid DH
17⍺-hydroxylase
17⍺-hydroxylase
17ß-hydroxysteroid DH
Aromatase
Finasteride mechanism of action
Inhibition of 5⍺-reductase which prevents the conversion of testosterone to the more active DHT
What is Congenital Adrenal Hyperplasia
Mutations in adrenal glands that prevents the synthesis of hormones and development of gonads
CAH mutations
3ß-hydroxysteroid DH
17⍺-hydroxylase
21⍺-hydroxylase
11ß-hydroxylase
Estrogen effect on disease
- increased exposure linked to some cancers
- low levels lead to osteoporosis
Testosterone effect on disease
- increased exposure linked to CV disease and CaP
- low levels: ED, more fat, insulin insensitivity, elevated TG, low HDL
Can steroid hormones pass through membranes?
Yes, they are lipid soluble
Corticosteroid Binding Globulin
Complexes with Cortisol to carry it through the blood
Sex Steroid Binding Globulin
Complexes with Testosterone and Estradiol to bring it through the blood
Estrogen Receptor mechanism
Estrogen enters cytosol and binds to ER, displacing a HSP
ER then travels to nucleus and binds to ERE and other co-activators to enhance transcription
Tamoxifen mechanism of action
Prevents ER from binding to coactivators by preventing conformational change
This then prevents transcription ie cancer
(only helps if the cancer is hormone-responsive)
- can also increase risk of uterine cancer bc coactivators can still bind even w/o conformational change