Steroids Flashcards
What are the 5 classes of steroid hormones
- Progestagens (C21)
- Glucocorticoids (C21)
- Mineralocorticoids (C21)
- Androgens (C19)
- Estrogens (C18)
What is the effect of angiotensin II on the adrenal gland
Stimulates the adrenal gland zona glomulerosa to produce aldosterone
What is the effect of ACTH on the adrenal gland?
Stimulates the release of cortisol from the zona fasciulata and androgens from the zona reticularis
What kind of receptor does angiotensin II act on
G-protein coupled receptor that activates phospholipase C, which converts PIP2 to DAG And IP3. DAG stimulates PKC and IP3 increases Ca2+ release from the ER
What kind of receptor does ACTH/FSH/LH act on
G-protein coupled receptor that activates adenylyl cyclase (leading to eventual activation of PKA)
What does this mean to you: SALT, SUGAR, SEX
Divisions of the adrenal gland, from outside to inside: 1. SALT: Zona glomerulosa produces aldosterone, “salt steroid” that controls water and electrolyte balance
- SUGAR: Zona fasciculata produces cortisol – “sugar steroid” that affects fuel metabolism and immune response
- SEX: Zona reticularis produces androgens – “sex steroids” that control development of male sexual traits
What are 3 things that occur when you don’t have enough glucocorticoids?
- Hypoglycemia: because cortisol usually inhibits insulin and stimulates glucagon.
- Weakness/fatigue: due to #1 and lack of normal gluconeogenic pathway
- Infections: natural control of inflammation gone
How does aldosterone help you maintain BP? What stimulates its release?
It increases Na+ (and its buddy H2O) reuptake and excretion of K+ in the distal tubules of the kidney, increasing blood volume and cardiac output. Its release it stimulated by angiotensin II, which senses low blood Na+ and high blood K+
What is the main mineralocorticoid?
Aldosterone
What does testosterone do? I know, its a soft ball. You got it
- Anabolic effects: muslce mass and bone growth
- Androgenic effects: 2’ sexual characteristics in males during puberty
- Promotes spermatogonia differentiation
Where is progesterone made, what does it do and what stimulates its release?
- Made in corpus luteum and placenta
- Prepares uterine lining during ovulation, maintains pregnancy
- Stimulated by FSH
What are 3 types of estrogens and what is their significance? Rate their potencies
- Estrodiol (E2): #1 in ovaries
- Estriol (E3): made in placenta
- Estrone (E1): major source of estrogens in post-menopausla women. Made in adipose and ovary and can serve as reservoir for estradiol
Potency: Estradiol>Esterone>Estriol
What is the precursor for ALL steroid hormones
Cholesterol (C27)
Where does the cholesterol that fuels all steroid synthesis come from?
- De novo synthesis from acetyl-coA in cytoplasm and ER
- Cholesterol ester droplets
- LDL
What enzyme catalyzes the rate limiting step in steroid synthesis? What is the product of this reaction?
Rate limiting enzyme: 20,22 desmolase aka side-chain cleaving enzyme
Reaction: cholesterol–> pregnenolone
What is the precursor for mineralocorticoid/glucocorticoid synthesis? What about sex hormone synthesis?
Mineralocorticoid/glucocorticoid: progesterone
Sex hormone: androstenedione
Describe testosterone synthesis. Ugh these questions are the worrrrst
- Cholesterol (C27) to pregnenolone (C21)
- Pregnenolone (C21) to DHEA (C19) by two different P450 enzyme reactions that replace the C17 aldehyde with a ketone, making it less active. Occurs in adrenals, ovaries, testes
- DHEA to androstenedione (C19). Ketone at C3
- Androstenedione to testosterone (alcohol at p17)
How is testosterone converted to estradiol?
- The A ring is aromatized and demethylated
- The ketone on C3 is converted to an alcohol (estradiOL is an alcohOL)
How is dihydrotestosterone (DHT) formed?
5a reductase can produce a more potent testosterone called dihydrotestosterone (DHT), which occurs in target tissues
How is estrone formed?
- Cholesterol (C27) to pregnenolone (C21)
- Pregnenolone (C21) to DHEA (C19) by two different P450 enzyme reactions that replace the C17 aldehyde with a ketone, making it less active. Occurs in adrenals, ovaries, testes
- DHEA to androstenedione (C19). Ketone at C3
- The A ring is aromatized and demethylated, and the C3 ketone is converted to an alcohol (still have ketone at C17 so estrONE is still a ketONE)
How is Aldosterone formed?
- Cholesterol (C27) to pregnenolone (C21)
- Pregnenolone to progesterone (C21)
- Progesterone to aldosterone through a series of P450 reactions that put an ALDehyde on C13
How is cortisol formed?
- Cholesterol (C27) to pregnenolone (C21)
- Pregnenolone to progesterone (C21)
- Progesterone to cortisol through 2 P450 enzyme reactions that puts alcohols on C11 and C17.
What is congenital adrenal hyperplasia and what is the most common form?
An autosomal recessive deficiency of steroid biosynthetic enzymes. Most common deficiency is CYP21.
What changes in steroid hormone levels will you see in CYP21 deficiency
- Increased progesterone (can’t convert to aldosterone or cortisol)
- Decreased Aldosterone
- Decreased Cortisol
- Increased androgens (all the pregnenalone is converted to DHEA)
What changes in steroid hormone levels will you see in CYP11β1 deficiency?
- Increased DOC (an intermediate in the aldosterone synthesis pathway).
- Over-activation of MC receptors by DOC causes hypertension (vasoconstriction)
- Decreased cortisol levels cause more ACTH release which increases DOC levels more
- Increase androgens
What changes in steroid hormone levels will you see in CYP17 deficiency?
- Decreased cortisol
- Increase aldosterone (more progesterone converted to aldosterone)
- Increased DOC (same as #2) (hypertension)
- Increased ACTH
What is a good way to suppress ACTH production and treat CAH?
Prednisone
