51-STEROID HORMONE METABOLISM (LECTURE #2 & 3) – Dr. Venk Flashcards
What is the second messenger that stimulates the synthesis and secretion of cortisol?
P-t450 hydroxylase enzymes.
What is the second messenger that stimulates the synthesis and secretion of aldosterone?
Phosphotidylinositol cascade.
Name the second messenger that is produced as a result of atrial natriuretic factor binding to kidney cells.
cGMP is the second messenger.
Guanylate cyclase catalyzes the formation of…
cGMP
Cholesterol esterase catalyzes the formation of…
cholesterol and fatty acids
The hormone that triggers synthesis and secretion of adrenal steroids is…
ACTH
Desmolase (20,22-lyase) catalyzes the formation of
pregnenolone
CYP is defined as _____.
CYP stands for genes that encode for cytochrome P450 hydroxylase enzymes.
The conversion of angiotensin I to angiotensin II is catalyzed by .
angiotensin converting enzyme (ACE)
In congenital adrenal hyperplasia, the enzyme that is deficient is …
CYP21A2 (cytochrome P450 steroid 21-hydroxylase
Adrenal insufficiency causes … disease
Addison’s disease
Name 2 reasons for Cushing’s syndrome.
Prolonged exposure to glucocorticoids caused by usage of anti inflammatory drugs or tumors of adrenal cortex.
Name an adrenal steroid that causes HTN upon its overproduction.
Mineralocorticoids, such as epinephrine, can cause HTN upon excessive secretion.
Name an aldosterone antagonist.
Spironolactone, cGMP, Lisinopril, Enalipril, and Captopril are aldosterone antagonists.
Name 2 competitive inhibitors of ACE.
Captopril, lisinopril and enalapril are competitive inhibitors of ACE.
Pregnancy is maintained by continuous secretion of progesterone, which is stimulated by the hormone …
LH
Describe how apoptosis is stimulated during the ovarian cycle.
Apoptosis is stimulated during ovarian cycle by the removal of the steroids estradiol and progesterone.
Testosterone to estradiol conversion is catalyzed by …
aromatase
Two hormones that stimulate luteolysis are …
oxytocin and PGF2α
Human placenta lacks the hydroxylase enzyme …
CYP17
Testicular feminization is the result of deficiency of …
5α-reductase
Cortisol is transported form site of synthesis (adrenal gland) to the target tissue by …
transcortin
Transcortin binds to …
the target tissue of cortisol
Testosterone is transported by …
testosterone-estrogen-binding protein (TEBP)
A plasma protein that binds nonspecifically to steroids is …
albumin
Name 2 compounds that inactivate steroids upon conjugation.
Glucouronides or sulfates can inactivate steroids in liver by conjugation.
Receptors for FSH, LH, GnRH, Angiotensin II and III are located on …
plasma membrane
Receptors for cortisol and aldosterone are located in …
the cell interior (cytosol)
Receptors for testosterone, estrogen and progesterone are located in …
the nucleus
What are heat shock proteins?
Heat shock proteins (hsp) are cytosolic proteins that occlude the DNA binding region of the cortisol and aldosterone receptors and cause the receptors to be inactive.
Define hormone response element.
Hormone response element is a region of DNA to which a hormone receptor complex can bind to and activate transcription.
Glucocorticoids cause the repression of .. gene.
proopiomelanocortin (POMC)
True or False: The active conformation of the steroid hormone receptor is a dimer.
False is a trimer.
Describe the DNA binding domain of hormone receptor.
The DNA binding domain of hormone receptors shares 60-95% homology between steroid receptor classes. They also contain Zn fingers.
What are Zinc fingers?
Zn fingers are secondary structures that are formed in the DNA binding domain that facilitate binding to DNA near the transcription initiation complex.
What are the secretion signals for aldosterone, cortisol, testosterone, 17beta-estradiol and progesterone respectively?
Aldosterone – hypovolemia and decreased Na+ concentrations.
Cortisol – low Na+
Testosterone – LH acting on the Leydig cells.
17-estradiol – a cAMP second messenger system, pregnancy.
Progesterone – the embryo (LH and human chorionic gonadotropin), pregnancy
Name the bone forming and bone resorbing cells.
osteoblast (bone forming)
ostoclast (bone resorbing)
Name some bone antiresorptive compounds.
bisphosphanates, alendronate (Fosamax) and Risedronate (Actonel)
Name a catabolic product of estradiol that induces breast cancer.
16-hydroxy estrogen (16-OHEN)
What are the compounds that are being used in hormone replacement therapy (HRT) treatment?
equine estrogen/medroxy progesterone (progestin)
Name the universal sulfonate donor compound.
PAPS - 3’ phosphoadenosine 5’-phosphosulfate
What happens if there is a deficiency in adrenal isoform of desmolase activity? Describe the clinical problems associated with this condition.
…
Describe the biochemical basis of Congenital adrenal hyperplasia.
Deficiency of cytochrome P450 steroid 21-hydroxylase (CYP21A2), results in congenital adrenal hyperplasia (CAH)
CAH causes high levels of ACTH, adrenal hyperplasia, decreased BP and increased progesterone.
Describe the biochemical basis of Addison’s.
Deficiency of adrenal steroid hormones (like cortisol and aldosterone). Lack of cortisol results in lack of negative inhibition feedback, thus ACTH levels are always high.
Describe the biochemical basis of Cushing’s syndrome
Overproduction of adrenal hormones result in prolong exposure to glucocorticoids (cortisol) results in hyperglycemia. Increased aldosterone leels result in hypertension.
Describe the biochemical basis of Hypertension.
Excessive secretion of minerolocorticoids.
Describe the biochemical basis of Osteoporosis.
Osteoporosis is due to the lack of estrogen.
Since estrogen induces the synthesis of osteoprotegrin, which causes osteoblast differentiation and suppresses ostoclasts activity, the lack of estrogen would cause osteoporosis.
Describe the biochemical basis of Testicular Feminization
deficiency in 5alpha-reductase results in the decreased ability to reduce testosterone into the more potent dihydrotestosterone (DHT)
Describe the role of fetal adrenal gland and fetal liver with reference steroid metabolism during pregnancy.
Because the human placenta lacks CYP17, it cannot synthesize estrogen from DHEA. The fetal adrenal gland, therefore, onverst the cholesterol to DHEA, which is transported to the fetal liver to form 16alpha-hydroxy-DHEA, that can be converted to estrogen by the placenta.
Describe the process of estradiol mediated programmed cell death.
The reduction of estradiol causes the cell to undergo apoptosis.
Describe atrial natriuretic factor (ANF) mediated cell signaling)
The Atrial Natriuretic Factor, ANF, binds to specific zona glomerulosa cell membrane receptors and activate guanylate cyclase. Guanylate cyclase catalyzes the formation of cGMP, which antagonizes the synthesis and secretion of aldosterone.
Describe the key enzymes of the steroid metabolism (generic name sufficient)
- 20-22 lyase (desmolase) ==> pregnenolone
- 21-hydroxylase ==> aldosterone and cortisol
- 5-alpha reductase ==> dihydrotestosterone
- aromtase ==> estradiol
Describe the mechanism of p-450 hydroxylase catalyzed reaction
A p-450 hydroxylase catalyzed reaction catalyzes the oxidation organic substances, like steroidal hormones. Most commonly, cytochrome 450 causes a MONOoxygenase reaction, which inserts one atom of oxygen onto an organic substrate while while the other oxygen atom is reduced to water.
