Steroid Biosynthesis

Question 1

Synthesis of steroid hormone begins with the rate limiting step that is catalyzed by ____ to produce ____.

Enhanced by ____.

Answer 1

Desmolase

Pregnenolon

ACTH, LH

Question 2

Pregnenolone is converted to ____ by _____ enzymes.

Answer 2

Progesterone

17-alpha-hydroxylase and 3-beta-hydroxysteroid dehydrogenase

Question 3

Glucocorticoids have a ____ affinity for mineralocorticoids and are ____ more concentrated

Answer 3

Higher

100

Question 4

What enzyme converts progesterone to aldosterone and cortisol?

Answer 4

21-alpha-hydroxylase

Question 5

17, 20-lyase aids in the formation of ____.

Answer 5

Estradiol and testosterone

Question 6

What hormone stimulates estradiol production in ovaries by activating the enzyme aromatase?

Answer 6

FSH

Question 7

21-hydroxylase deficiency causes what?

Symptoms?

Answer 7

Decrease production of aldosterone and cortisol

Hyponatremia, hypotension, hypoglycemia

Causes virilism (male secondary sex characteristics) in females because increased flow if intermediates into adrenal androgens

Question 8

Classical congenital adrenal hyperplasia due to ____ deficiency.

Can be associated with Turner’s Syndrome because of decreased estradiol levels leading to increase FSH and LH.

Turner’s syndrome is due to a deleted ___ chromosome and have symptoms such as ____.

Answer 8

21-hydroxylase

X (45XO)

Streak ovaries

Question 9

Deficiency of 17-alpha-hydroxylase cause as what?

Defect in 11-beta-hydroxylase causes what?

Answer 9

Loss of cortisol and sex steroids

Hypertension because accumulation of 11-decoxycorticosterone (has mineralocorticoid activity

Question 10

Cortisol is metabolized to cortisone through the action of 11beta-hydxroxysteroid dehydrogenase. This is inhibited by what? Causing what?

Cortisone has a ___ affinity to mineralocorticoids.

Answer 10

Licorice

Hypertension due to salt retention

Lower

Question 11

Active form of vitamin D?

Acts through ____ receptors targeting genes containing _____.

Answer 11

Calcitriol (1,25-dihydroxycholecalciferol)

Nuclear receptors

Vitamin D response element (VDRE) sequence

Question 12

Describe vitamin D synthesis

Sources? Enzymes? Location?

Answer 12

Skin has 7-dehydrocholesterol -> exposed to sunlight -> converted to cholecalciferol (inactive vitamin D) -> converted to 25-hydroxyvitamin D by 25-hydroxylase in the liver

Ergocalciferol is another source of vitamin D in the intestine

In the kidney 1,25-dihydroxycholecalciferol (calcitriol) is synthesized by 1-alpha hydroxylase

Question 13

25-hydroxycholecalciferol is hydroxylated in the ____ of the kidneys by ____ enzyme.

This generates ____.

The action of this enzyme is stimulates by ____ and low Pi; inhibited by ____

Answer 13

Proximal tubules

1-alpha-hydroxylase

Calcitriol

PTH; calcitriol

Question 14

Women with congenital adrenal hyperplasia have what symptoms?

Fetus at risk will have excess ___ in amniotic fluid.

Treatment of adrenal hyperplasia?

Answer 14

Hirsutism: excess body hair

General oligomenorrhea: infrequent menstruation; greater than 35 days; infertility

Excess cortisol

Hormone replacement therapy (HRT)

Question 15

Male pt with hypertension, normal genitalia or female with ambiguous genitalia present with low aldosterone, low cortisol, high testosterone, has elevation in what enzyme?

Why?

Answer 15

11-deoxycorticosterone

11-hydroxylase deficiency leading to inability to synthesize aldosterone and causing build up of mineralocorticoid 11-deoxycorticosterone (buildup is causing the hypertension)

Question 16

____ enzyme deficiency presents in a male with ambiguous genitalia due to decreased production of testosterone

_____ enzyme deficiency presents with low levels of serum mineralocorticoids and low BP. Testosterone is elevated

Answer 16

17-hydroxylase

21-hydroxylase (Cyp21A2)

Question 17

Accumulation of progesterone and 17-hydroxyprogesterone are due to a deficiency of what enzyme?

Answer 17

21-hydroxylase (Cyp21A2)

Question 18

Accumulation of 11-deoxycorticosterone and 11-deoxycortisol is a result of what enzyme deficiency?

This enzyme is normally stimulated by what?

Answer 18

11-beta hydroxylase

Angiotensin II

Question 19

Progesterone is converted into ____ which is a mineralocorticoid that binds to a MR receptor.

Excessive levels of this mineralocorticoid causes ____ syndrome.

Answer 19

Aldosterone

Conn syndrome -> increased blood volume and hypertension

Question 20

Describe the hormonal pathway of ACTH

Answer 20

Cortisol levels fall -> hypothalamus produces CRH -> stimulates anterior pituitary to release ACTH -> simulates adrenal gland -> activates desmolase to begin the break down of cholesterol to cortisol

Question 21

How does ACTH act on the adrenal cortex (zona fasiculata)?

How does a tumor form through this mechanism?

Answer 21

Binds to cell surface ACTH receptors (g-protein-coupled receptor)

Activates PKA through cAMP

Stimulates glucocorticoid steroid hormone synthesis and secretion

Tumor cells have uncoupling of G cells to receptor, yet PKA is always on, signaling cell proliferation

Question 22

How does ACTH influence steroid hormone secretion?

Answer 22

Rapid short-term mechanisms

Stimulation of cholesterol delivery to the mitochondria where P450 (CYP) enzyme is located; this catalyzes the first step of steroidogenesis (cleave side chain of cholesterol)

Question 23

Long-term effects of ACTH

Answer 23

Stimulates lipoprotein uptake into cells

Increases bioavailability of cholesterol in adrenal cortex

Stimulation of the transcription of the genes coding for steroidogenic enzymes

Question 24

Mutations in ____ enzyme produce pseudohermaphroditism and adrenal hyperplasia

This enzyme is key in the steroidogenic pathway

Answer 24

17, 20 -lyase

Question 25

Which form of vitamin D requires sunlight for its formation?

Answer 25

Cholecalciferol