Steroid Biosynthesis

Question 1

What is the significance of progesterone?

Answer 1

Supports pregnancy and embryogenesis. It prepares the uterus for implantation and relaxes smooth muscle and decreases the maternal immune response

Question 2

What happens to levels of progesterone before menstruation labor and lactation?

Answer 2

It decreases

Question 3

What is desmolase?

Answer 3

enzyme that produces pregnenolone from cholesterol

Question 4

What hormone regulates desmolase activity?

Answer 4

ACTH, it stimulates production of pregnenolone from cholesterol

Question 5

Where is Desmolase found and what type of enzyme is it?

Answer 5

Found in steroid producing tissues and it is also known as Cytochrome P450

Question 6

What is the most important biochemical intermediate that is used as a substrate to produce other steroid hormones?

Answer 6

Pregnenolone

Question 7

What hormones can pregnenolone be used to make?

Answer 7

Progesterone Aldosterone Cortisol Testosterone Estradiol

Question 8

What specific carrier protein carries most of the plasma glucocorticoid hormones and progesterone?

Answer 8

Corticosteroid binding globulin, it belongs to the serine inhibitor family of proteins

Question 9

What releases renin?

Answer 9

Kidneys when low blood volume is detected

Question 10

What does Renin do?

Answer 10

cleaves angiotensinogen from the liver into angiotensin I

Question 11

What enzyme converts angiotensin I into angiotensin II?

Answer 11

ACE

Question 12

What does aldosterone do and what triggers its release?

Answer 12

Angiotensin II stimulates release of vasopressin from pituitary and aldosterone from adrenal cortex. It acts on kidneys to cause an increase in Na and water resorption to increase BP

Question 13

What receptor does aldosterone bind & activate?

Answer 13

Mineralocorticoid receptor, a nuclear receptor superfamily member

Question 14

What two hormones binds with the highest efficacy to MR?

Answer 14

Highest is aldosterone and next highest is 11-deoxycorticosterone

Question 15

What hormones can increase Na retention therefore increasing blood pressure?

Answer 15

Aldosterone 11-Deoxycorticosterone Testosterone Hydrocortisone Corrtisone

Question 16

Primary aldosteronism?

Answer 16

Excessive levels of aldosterone from the adrenal glands, leads to conn syndrome. This leads to high blood pressure and can causes a loss of K and retention of Na

Question 17

4 hallmarks of Conn syndrome?

Answer 17

Excessive secretion of aldosterone Retention of Na Loss of K Produces Htn

Question 18

What causes adrenal hyperplasia?

Answer 18

Classic and non classic forms, both caused by deficiencies in adrenal enzymes used to synthesize glucocorticoids. Results in increased [production from adrenal gland of cortisol precursors and androgens

Question 19

Mild congenital adrenal hyperplasia can result in:

Answer 19

life threatening sinus infections Life threatening pulmonary infections shortened stature orthostatic syncope Severe acne

Question 20

How will a woman with mild congenital adrenal hyperplasia present?

Answer 20

• Hirsutism, excessive body hair on parts of body where hair is normally absent or minimal
• General oligomenorrhea, infrequent or light menstruation
• Infertility

Question 21

How do you tell if a fetus is at risk for congenital adrenal hyperplasia?

Answer 21

You can use HLA haplotype or test amniotic fluid for excess cortisol precursors

Question 22

How do you treat congenital adrenal hyperplasia?

Answer 22

Hormone replacement therapy

Question 23

What accumulates if you have a deficiency of 21-hydroxylase?

Answer 23

Progesterone and 17-Hydroxyprogesterone build up

• 21-hydroxylase will convert progesterone and 17OH-progesterone into Aldosterone and Cortisol down the road

Question 24

What happens if you have a deficiency of 11-B Hydroxylase?

Answer 24

Build up of 11-deoxycorticosterone and 11-deoxycortisol and lack of aldosterone and cortisol

• 11B hydroxylase will convert deoxycorticosterone and 11-deoxycortisol into aldosterone and cortisol

Question 25

Patient has a deficiency in 11-B hydroxylase, but they have high blood pressure. How does this occur?

Answer 25

• With this deficiency there is a decrease in the amount of aldosterone and cortisol produced
• However, there is a build up of 11-deoxycorticosterone and 11-deoxycortisol and these have mineralocorticoid effects and can produce hypertension
  
  • 11-deoxycorticosterone have high affinity for MR receptor

Question 26

What are the biochemical steps for ACTH stimulating a process?

Answer 26

• Binds 7TM receptor and it undergoes the GPCR changes
• Stimulates adenylyl cyclase
• Increasing cAMP
• Activating PKA

Question 27

What is the significance of CYP17A1?

Answer 27

• Has 17a-hydroxylase and 17,20-lyase enzyme activities
• produces progesterins mineralocoertioids glucocorticoids androgens and estrogens
• It is a drug target for prostate cancer

Question 28

How does CYP17A1 relate to prostate cancer?

Answer 28

• It can have a rare deficiency where there is defecient production of androgens resulting in 46XY disorders of sex dev.
• Production of glucocorticoids is good
• Several missense mutations in CYP17A1 cause this condition

Question 29

What enzyme synthesizes 1,25-dihydroxycholecalciferol and where?

Answer 29

1-a hydroxylase in the kidney

Question 30

What form of Vitamin D is exclusively found in the liver?

Answer 30

25-hydroxycholecalciferol