Steroid Biosynthesis

Question 1

In general hydrophobic ligands and signals have high or low affinity for it’s receptors?

Answer 1

High affinity. Concentration of ligand in bloodstream is low.

Question 2

True or False. Steroid hormones are transcription factors

Answer 2

True. they bind to hormone and to DNA.

Question 3

What is the precursor for steroid hormones?

Answer 3

Cholesterol.

Question 4

Steroid hormones are synthesized in what organelle of which organs/glands?

Answer 4

smooth ER of adrenal cortex, ovaries, and testes.

Question 5

Where do steroid hormone producing organs get their cholesterol from?

Answer 5

1. circulating LDL
2. de novo synthesis from acetyl CoA
3. cholesterol ester stored in cytoplasmic lipid droplets

Question 6

What is the rate limiting step of steroid hormone synthesis?

Answer 6

Conversion of cholesterol to pregnenolone done by the enzyme Desmolase which adds carbonyl group on the D ring of cholesterol and cleaves off a six-carbon piece of its side chain.

Question 7

Pregnenolone can be converted to progesterone via the enzyme 3-b-hydroxysteroid dehydrogenase. Progesterone can then be converted in a tissue specific manner. Where are the following made: Aldosterone, cortisol, estradiol, and testosterone.

Answer 7

Aldosterone - zona glomerulosa
cortisol - zona fasciculata
estradiol - in ovaries and some in adrenal cortex
Testosterone (from adnrogen) and from more potent dihydroterstosterone in testes and minor amount in adrenal cortex.

Question 8

Pregnenolone, besides being a precursor to a bunch of steroid hormones, is also a modulator of neurotransmitter signaling in the brain. What receptor in the brain does it effect that which is involved in memory and learning, and is used as a treatment thought to help in multiple neurological disorders.

Answer 8

NMDA receptors.

Question 9

Progesterone supports gestation and embryogenesis and is involved in menstrual cycle. During menstruation, labor, and lactation, what happens to progesterone levels, increase or decrease?

Answer 9

Decreases

Question 10

In preterm neonates, giving mothers a dose of which steroid hormone can help the neonate overcome IRDS

Answer 10

glucocorticoids

Question 11

How does glucocorticoids act as an immunosuppresion?

Answer 11

By inhibting both cellular and humoral immune response. They induce production of i-kBa inhibitory proteins which inactivates NF-kB which synthesizes many pro-inflammatory cytokines like IL2 which is needed for T cell proliferation. Decreased IL2 and its receptors lead to an inhibition of clonal expansion of B cells as well. Cortisol promotes T cell apoptosis.

Question 12

Which enzyme is only found in tissues that produce steroid hormones (gonads and adrenal cortex) and is a p450 family of monooxigenase and its’ expression and activity is stimulated by peptide hormones.

Answer 12

Desmolase.

Question 13

which peptide hormones have stimulatory effect on desmolase?

Answer 13

ACTH, LH, and FSH

Question 14

In the ovaries FSH is a direct stimulator for which enzyme?

Answer 14

Aromatase which produces estrone from androstenedione; and estradiol from testosterone

Question 15

Progesterone is a negative feedback inhibitor for which structures?

Answer 15

Hypothalamus and pituitary.

Question 16

During mid follicular phase, is progesterone and estradiol inhibitory or stimulatory for the pituitary to produce FSH and LH?

Answer 16

inhibitory

Question 17

During Late follicular phase estradiol (stimulates or inhibits) pituitary to release FSH and LH.

Answer 17

stimulates.

Question 18

FSH and LH are stimulator or inhibitor for estradiol during ofllicular phase?

Answer 18

stimulator

Question 19

FSH and LH are stimulator or inhibitor for progestogen during luteal phase?

Answer 19

stimulator

Question 20

A common inherited defect in which enzyme will lead to salt wasting, hypotension due to decrease production of aldosterone, and hypoglycemia due to decreased production of coritsol?

Answer 20

21-hydroxylase

Question 21

In female, deficiency of which enzyme causes virilism (develoment of male secondary characteristics) due to an icnreased flow of intermediates into the adrenal androgens?

Answer 21

21 hydroxylase

Question 22

In a rare deficiency of this enzyme will cause loss of cortisol as well as sex steroids, but the decrease in cortisol is compensated for by increased production of cortisosterone.

Answer 22

17-a-hydroxylase

Question 23

Hypertension is caused by accumulation of 11-decoxycoricosterone, as seen in defect of this enzyme.

Answer 23

11-b-hydroxylase.

Question 24

Explain MOA for finastride which is used as a treatment for benign prostatic hyperplasia.

Answer 24

Normally androgenic potency of testosterone is amplified by its conversion to dihydrotestosterone (DHT) mediated by 5a-reductase. DHT has a much higher affinity for androgen receptors. Finasteride is an inhibitor for 5a-reductase and so prevents this potentiation. Tamoxifen (estrogen) works the same way.

Question 25

Explain MOA for finastride which is used as a treatment for benign prostatic hyperplasia.

Answer 25

Normally androgenic potency of testosterone is amplified by its conversion to dihydrotestosterone (DHT) mediated by 5a-reductase. DHT has a much hgiher affinity for androgen receptors. Finasteride is an inhibitor for 5a-reductase and so prevents this potentiation.

Question 26

What is the active form of Vitamin D?

Answer 26

Calcitriol - 1,25 dihydroxycholecalciferol

Question 27

Vitamin binds to a nuclear receptors, cytosolic receptor, or a cell surface receptor?

Answer 27

Nuclear receptor. It’s not a steroid, but it acts like one.

Question 28

In the liver cholecalfierol is converted to 25-hydroxycholecaliferol via what enzyme?

Answer 28

25, hydroxylase

Question 29

In the kidney 25-hydroxycholecalciferol is converted to 1,25, dihydroxycholecalciferol via what enzyme and what can inhibit or stimulate that enzyme?

Answer 29

1a-hydroxylae.

Stimulated by: PTH or low PO4. It can be inhibited by Calcitriol.

Question 30

What are the actions of calcitriol?

Answer 30

1. Stimulate intestinal cells to increase absorption of Ca and phosphate from the intestinal lumen.
2. increase reabsorption of Ca by the kidneys
3. promote resorption of ca from bone
   Net result: increase blood Ca and phosphate levels.