Lecture 29: Steroid Biosynthesis Flashcards
Why is progesterone important in pregnancy?
It regulates voltage Ca2+ channels on spermatozoa, prepares uterus for implantation, causes SM relaxation and decreases maternal immune response
What role do glucocorticoids play on infant respiration?
Glucocorticoid surge during delivery to enhance surfactant production
impaired process in premies leading infant respiratory distress syndrome
How do tissues limit Na/H2O retention?
Why does licorice stimulate Na/H2O retention?
- Since glucocorticoids induce Na/H2O retention, the tissues metabolize them to cortisone to block the glucocorticoid receptor and block retention
- Licorice has isoflavones that inhibit 11B dehydrogenase which turns cortisol to cortisone
What major pathways depend on cholesterol?
- Vitamin D3 (from 7 dehydrocholesterol)
- Steroid hormone synthesis
- Steroid degradation
- Bile acid biosynthesis
Draw the pathway of steroid hormone biosynthesis in the adrenal cortex
Ok
What hormone induces steroid biosynthesis?
ACTH (induces conversion of cholesterol to pregnenolone)
What is the rate limiting enzyme of steroid biosynthesis and what is the major mechanism?
desmolase (removes 6 carbons from cholesterol and replaces with carbonyl group)
What steroid hormones can be synthesized from pregnenolone?
Progesterone, Aldosterone, Cortisol, Testosterone, Estradiol
What proteins transport steroid hormones in the blood and what do they specifically transport?
CBG - most glucocorticoids + progesterone
SHBG and albumin - sex hormones (Testosterone, DHT, Estradiol)
Review: Be able to draw the RAAS pathway and the effects of ACE inhibitors and vasopressin
Ok
What is the main defect in Adrenal Hyperplasia?
What is the main treatment?
- deficiency in 21 hydroxylase or 11B hydroxylase leading to accumulation of hormone precursors in affected pathway
- hormone replacement therapy
How do adrenal hyperplasia patients present?
hirsutism, general oligomenorrhea (infrequent/light menses), infertility
How would you test a fetus for risk in developing congenital adrenal hyperplasia?
- Human leukocyte antigen (HLA) haplotype test
2. Presence of excess cortisol precursors in the amniotic fluid
AH due to 21- hydroxylase (Cyp21A2) deficiency
AH due to 11-B hydroxylase (Cyp11B1) deficiency
- leads to accumulation of progesterone and 17-hydroxyprogesterone
- accumulation of 11 deoxycorticosterone and 11-deoxycortisol (also a mechanism of hyperaldosteronism)
What receptor is important for aldosterone to mediate its effects on target cells in the adrenal gland?
Mineralocorticoid receptor (MR) - part of a receptor superfamily that binds steroid hormones in the nucleus
What is Conn Syndrome?
excessive secretion of aldosterone > overstimulation of zona glomerulosa > too much Na and water retention = HTN
What hormones can also activate MR and cause Na retention (thus high BP)?
11 deoxycorticosterone
testosterone
hydrocortisone (cortisol)
cortisone
How does 11-B hydroxylase deficiency cause HTN?
- accumulation of 11-deoxycorticosterone and 11-deoxycortisol > both bind the MR receptor like aldosterone > increase HTN
- basically the products that accumulate have capabilities of mimicking aldosterone effects because they bind the same receptor
How do glucocorticoids cause immunosuppression?
they induce i-kBa which makes NF-KB inactive
Review: Be able to draw the HPA axis
Ok
What is the mechanism of ACTH?
ACTH > binds to ACTH receptors on adrenal cortex cells > Gs > AC > cAMP > PKA > phosphorylation of CREB > cell proliferation and cortisol production in target cell
What happens to ACTH signaling in tumor cells?
-stimulation of proliferation and cortisol production even without ACTH stimulation > process in constantly turned on
What are the short term (within minutes) actions of ACTH?
What are the long term (within several hours) actions of ACTH?
- cholesterol taken to MT where desmolase is
- gene transcription of enzymes needed for aldosterone and cortisol synthesis
What is 17,20 lyase (CYP17A1) deficiency?
-associated with 17,20 lyase and 17a hydroxylase deficiency > testosterone synthesis pathway blocked > leading to pseudohemaphroditism and adrenal hyperplasia
Review: Be able to draw the pathway of Vitamin D synthesis
Ok
