Steroid Biosynthesis

Question 1

C21 steroids

Answer 1

• Progestins-progesterone, pregnenolone
• Glucocorticoids- cortisol, corticosterone
• Mineralorcorticoids- aldosterone, 11-deoxycorticosterone

NOTE: C21 steroids with OH at C17 are called 17- hydroxysteroids

Question 2

C19 Steroids

Answer 2

Androgens-testosterone, androstenedione, DHEA, DHT

Question 3

C18 steroids

Answer 3

Estrogens- Estradiol, estrone, estriol

Question 4

Conversion of cholesterol to pregnenolone is by ____________ enzyme.

Answer 4

Side-chain cleavage enzyme (CYP 11A1)

NOTE: This occurs in the inner mitochondrial membrane and this step is rate-limiting for steroidogenesis.

Question 5

Most steroidogenic enzymes belong to the ________ family and are thus reffered to as CYPs.

Answer 5

P-450 monooxidase gene family

Question 6

Aldosterone is inhibited by ________.

Answer 6

ANP

NOTE: Aldosterone is stimulated by angiotensin II, high potassium, and acutely elvated ACTH.

Question 7

___________ cataylzes the last 3 reactions fro 11-deoxycorticosterone (DOC) to aldosterone.

Answer 7

Aldosterone synthase (CYP11 B2)

*This enzyme is unique to the zona glomerulosa

Question 8

What role does ACTH play in the transport of cholesterol?

Answer 8

ACTH increases the number of adrenocotical cell receptors for LDL

NOTE: ACTH also increases de novo synthesis of cholesterol from acteyl CoA (primarily catalyzed by cholesterol esterase hydroxylase a.k.a hormone sensitive lipase)

Question 9

Which hormones is necessary for the formation of cortisol?

Answer 9

CYP 17 17 a-hyroxylase

Question 10

Cortisol is reversibly inactivated to cortisone by _______.

Answer 10

11b-hydroxysteroid dehydrogenase Type 2

NOTE: This serves to protect mineralocorticoid receptors in aldosterone responsive cells

Question 11

__________ converts cortison back to cortisol in tissues expressing the glucocorticoid receptor.

Answer 11

11b-HSD1

Question 12

_________________ inhibits CYP11B1.

Answer 12

Metyrapone

Question 13

Corticosteroids and their relative glucocorticoid and mineralocorticoid activities compared to cortisol

Answer 13

Question 14

Cushing’s syndrome

Answer 14

A constellation of clinical abnormalities caused by chronic high levels of cortisol or related corticosteroids

• Central obesity
• Hirsuitism
• Hypocalcemia
• Hyperpigmentation
• Metabolic syndrome

Question 15

Cushing’s disease

Answer 15

Excess pituatary production of ACTH, generally secondary to a pituitary adenoma

Question 16

What enzyme is unique to the zona reticularis?

Answer 16

17,20 lyase (CYP 17)

NOTE: The major androgen secreted by the zona reticularis is DHEA

Question 17

________ inhibits cholesterol side-chain cleavage enzyme, 17a-hydroxylase and 17,20 lyase activity.

Answer 17

Ketoconazole

Question 18

____________ deficiency accounts for 90% of all congenital adrenal hyperplasia cases.

Answer 18

21 B- Hydroxylase

NOTE: If there is a 21 B- hyrdroxylase deficiency 17-OH Progesterone will be elevated, which will lead to an elevation in androgen secretion.

Question 19

Treatment for congenital adrenal hyperplasia

Answer 19

• Long-term glucocorticoid or aldosterone replacement (or both)

Question 20

What is the major difference between congenital adrenal hyperplasia as result of 11B-hydroxylase deficiency as opposed to 21- B- hydroxylase deficiency?

Answer 20

Hypertension along with hypokalemia

NOTE: It should be treated with glucocorticoids

Question 21

Testosterone synthesis from cholesterol can take four pathways, the _____ pathway is preferred.

Answer 21

D5

Question 22

Human testes secrete a small portion of DHT. Most DHT is derived from peripheral conversion of testosterone by __________.

Answer 22

5a-reductase type 2

Question 23

Human testes make small, but significant amounts of 17b-estradiol. Most E2 comes from peripheral _________ of androstenedione and testosteron.e

Answer 23

Aromatization

Question 24

17B hydorxysteroid dehyrogenase (TYPE 3) mutation is caused by mutations in the _______ gene.

Answer 24

HSD17B3

*Autosomal receissive

NOTE: It is clinically indistinguishable from androgen insensitivity syndrome in prepubertal patients

Question 25

5a- reductase deficiency

Answer 25

• Genetic males are born with ambiguous genitalia
• Clinical abnormalities range from infertility with normal male anatomy to underdeveloped male anatomy with hypospadias to predominant female genitalia

Question 26

CYP19 is also known as __________

Answer 26

AROMATASE

Question 27

Two cell model of Steroidogenesis in the dominant ovarian follicle

Answer 27

Question 28

The liver convers estradiol and estrone to _______.

Answer 28

Estriol

NOTE: Hepatic enzymes add glucuronide or sulfate moieties for excretion in the bile

Question 29

The major metabolite of progesterone is ___________, which is conjugated with glucuronide and excreted in urine.

Answer 29

Pregnanediol

Question 30

_______________ convert cortisol to cortisone.

Answer 30

Syncytiotrophoblasts

NOTE: Syncytiotrophoblasts lact CYP17

Question 31

Progesterone synthesis in the placenta

Answer 31

NOTE: The 1st step with side chain cleavage enzyme is NOT rate-limiting.

Question 32

Why is estriol a marker of fetal well-being?

Answer 32

If levels of unconjugated estriol are abnormally low in a pregnant woman, this may indicate chromosomal or congenital anomalies like Down syndrome or Edward’s syndrome.

Also determines fetal liver function