9. Steroid Biosynthesis Flashcards
What are secreted by the testis in response to FSH and LH respectively?
FSH stimulates inhibin.
LH stimulates testosterone.
What enzyme is “the gatekeeper” between progesterone and testosterone?
17,20-lyase.
What enzyme catalyzes the rate limiting step of steroid hormone biosynthesis?
Desmolase
What inhibits gonadotropin releasing hormone from the hypothalamus in males and females respectively?
Males: testosterone.
Females: progesterone.
In a patient with congenital adrenal hyperplasia, what is the result of a 17α-hydroxyprogesterone buildup?
Which versions of congenital adrenal hyperplasia could this be?
Excess androgen production, especially testosterone and dihydrotestosterone.
11β-hydroxylase deficiency/mutation.
95% of congenital adrenal hyperplasia involves which gene?
The other 5% involves what gene?
21-hydroxylase.
11β-hydroxylase.
How does adrenocorticotropic hormone increase the production of steroid hormones?
ACTH upregulates desmolase.
What are the symptoms associated with congenital adrenal hyperplasia?
Hirsutism.
General oligomenorrhea.
Infertility.
Simple virilizing.
Salt wasting (with dehydration, vomiting, and diarrhea).
(Non-classical is milder, and may cause only precocious puberty.)
What receptor is bound and activated by cortisol?
The glucocorticoid receptor.
What enzyme is upregulated by luteinizing hormone?
Desmolase.
Describe the regulation of desmolase.
Desmolase is upregulated by ACTH and LH.
What is the significance of glucocorticoids in premature infants?
A burst of glucocorticoids during delivery stimulates the production of surfactant.
How are follicle stimulating hormone and luteinizing hormone inhibited from the pituitary gland in males?
Inhibin inhibits follicle stimulating hormone.
Testosterone inhibits luteinizing hormone.
What are the short and long-term effects of adrenocorticotropic hormone?
Short-term: stimulates lipoprotein uptake into cortical cells and increases bioavailability of cholesterol in the adrenal cortex. (Brings the building blocks for steroid hormone synthesis)
Long-term: stimulates the transcription of the genes coding for steroidogenic enzymes.
What are the general functions of cortisol?
↑ Gluconeogenesis.
↑ Blood pressure.
↓ Inflammation.
What symptoms do we see in patients with 21-hydroxylase deficient congenital adrenal hyperplasia?
Salt wasting, due to lack of aldosterone.
Ambiguous genitalia in females.
How are follicle stimulating hormone and luteinizing hormone inhibited from the pituitary gland in females?
Progesterone inhibits follicle stimulating hormone and luteinizing hormone.
Estradiol inhibits FSH and LH in the early to mid follicular phase, but stimulates FSH and LH in the late follicular phase.
What enzyme is stimulated by follicle stimulating hormone?
What reactions are catalyzed by this enzyme?
Aromatase
Androstenedione -> Estrone
Testosterone -> Estradiol
What are the two steroid hormone blood transporter proteins mentioned in this lecture?
Where are they made?
Corticosteroid binding globulin (CBG).
Sex steroid binding globulin (SHBG).
They are made in the liver.
Where is cholecalciferol converted to 25-hydroxycholecalciferol?
What enzyme facilitates this reaction?
In the liver.
25-hydroxylase.
What receptor is bound and activated by testosterone?
The androgen receptor.
What receptor is bound and activated by aldosterone?
The Mineralcorticoid receptor
How are estradiol and progesterone stimulated to be released from the ovaries?
FSH and LH stimulate estradiol production in the follicular phase, and progesterone production in the luteal phase.
What two corticosterone precursors are increased in congenital adrenal hyperplasia due to 11β-hydroxylase deficiency?
11-deoxycorticosterone
17α-hydroxyprogesterone
In a patient with congenital adrenal hyperplasia, what would be the effects of a buildup of 11-deoxycorticosterone?
Which version of congenital adrenal hyperplasia would this be?
11-deoxycorticosterone acts on aldosterone receptors in an unregulated fashion, increasing sodium uptake, water retention, and potassium excretion.
This would be 11β-hydroxylase deficiency/mutation.
What reaction is catalyzed by desmolase?
Cholesterol -> pregnenolone.
What are the general functions of aldosterone?
↑ Na+ and H2O retention
↑ Blood pressure
What three compounds build up in patients with 21-hydroxylase deficient congenital adrenal hyperplasia?
Progesterone.
17α-hydroxypregnenolone.
17alpha-hydroxyprogesterone.
What are the primary symptoms of 17,20-lyase deficient congenital adrenal hyperplasia?
Males: pseudohermaphroditism, underdeveloped genitalia.
Both sexes: reduced or absent puberty, lack of development of secondary sexual characteristics, childlike appearance in adulthood if left untreated.
[Note: 17,20-lyase deficiency alone does not affect mineralcorticoid or glucocorticoid production. For that reason it does not cause adrenal hyperplasia or hypertension.]
