PHRM 825 Lecture 10: Synthesis of Steroids

juxtacrine signaling

direct physical contact

endocrine signaling

travels far through the blood, low in concentration and high affinity at receptor

minutes to hours

paracrine signaling

travels a short distance, high local concentration but low affinity

synaptic/ neuronal signaling

neurotransmitter, travels short distance, high local concentration that dissociates rapidly

autocrine signaling

made and functions in the same cell

similar to paracrine

know structure + numbering of cholesterol!

sex and progestational hormones

progesterone, 17B-estradiol, testosterone

female menstrual cycle, pregnancy, embryogenesis

progesterone (C-21)

estrogen, female hormone

17B- estradiol (C-18)

androgen, male hormone

testosterone (C-19)

adrenocoritcal hormones

cortisol, aldosterone

glucocorticoid, anti-stress hormone, anti-inflammation

cortisol (C-21)

mineralocorticoids, regulator of Na+ uptake in the kidney; raises BP and blood volume

aldosterone (C-21)

explain the negative feedback loop leading to the release of cortisol

stress triggers the hypothalamus which releases CRH--> triggers pituitary gland to release ACTH --> triggers adrenal gland to release cortisol

CRH

corticotropin-releasing hormone; hypothalamus

ACTH

Adrenocorticotropic hormone (from the pituitary gland)

what enzyme converts cholesterol to pregnenolone and what does it do

P450scc, cleaves large side chain and adds an acetyl group in its place

what are the three hormones that stem from pregnenolone

progesterone, cortisol, testosterone

3b-dehydrogenase action

converts alcohol to a ketone at the bottom of the molecule and moves double bond into aromatic ring attached to ketone

17a- Hydroxylase action

adds OH group to 17th carbon with the acetyl group

which hormone does not require the use of 17a hydroxylase or 17,20 lyase

pregnenolone--> progesterone --> aldosterone

what is the cause and results of 17-a hydroxylase deficiency

caused by mutations in CYP17A1

leads to overproduction of mineralocorticoids and deficiency of corticosteroids and sex hormones

symptoms of 17a hydroxylase deficiency

hypocortisolism- enlargement of adrenal glands

ambiguous genitalia

hyperaldosteronism- hypertension

cause and symptoms of 21- hydroxylase deficiency

mutations in CYP21A2

hypocorticolism

hypoaldosteronism- hyponatremia (lose sodium)

premature androgen exposure

which hormones are not affected by 21- hydroxylase deficiency

androstenedione, testosterone, estradiol

transported by corticoid binding globulin

glucocorticoids and progesterone

transported by sex hormone binding globulin

testosterone and estradiol

what is the difference between the testosterone and 17B- estradiol structure

estradiol has an aromatic ring with a hydroxy group at the bottom and testosterone has a ketone and one double bond at the bottom like progesterone

inhibits aromatase and P450scc

used to block steroid production in some hormone dependent tumors

Aminoglutethimide (cytadren)

anti fungal at lower concentration

inhibits P450scc, 17a-hydroxylase, and 11B- hydroxylase

can treat hyperglucocorticoid states

ketoconazole (nizoral)

excreted in bile

estrogen

excreted in urine

progesterone, androgen, and glucocorticoids