9. Steroid Hormone Biosynthesis

Question 1

Steroid hormones are derived from what?

Answer 1

cholesterol

Question 2

What is the path from of steroid synthesis?

Answer 2

Cholesterol (27 carbons) -> pregnenolone (21 carbons) via desmolase.

Pregnenolone -> progesterones (THE PRECURSOR TO ALL STERIODS)

Progesterones -> corticosteroids (cortisol and aldosterone) and sex hormones (testosterone (19) and estradoil (18))

Question 3

What are the other names for desmolase?

Answer 3

• 20, 22 Desmolase
• Cytochome P450scc
• CYP11a1

Question 4

Where is desmolase found?

Answer 4

all steroid producing tissue (adrenal, testes, ovaries and placenta)

Question 5

What catalzyes the 1st and rate-limiting step of steroid hormones

Answer 5

desmolase

Question 6

Desmolase is positively regulated by ____________.

Answer 6

ACTH

& LH

Question 7

What are the short-term and long-term actions of ATCH?

Answer 7

Short term: stimulate lipoprotein uptake in cortical cells and increases availability of cholesterol in the adrenal ctx

long term: transcribe genes that code for steroid hormones such as, cytochrome p450scc, which catalyzes the 1st step of steroidogenesis

Question 8

How is ACTH in a cancer cell?

Answer 8

• In a normal cell, ACTH will bind to Gs GCPR: +AC -> cAMP -> PKA to produce cortisol.
• In tumor cells, the proportion of cortisol is uncoupled from ACTH.
• Constituively active PKA will continue to make cortisol even w/o ACTH binding

Question 9

To go from progesterone -> aldosterone, what CYPS are needed

Answer 9

CYP21

CYP11B1

CYP11B2

these are types of cytochrome P450s

Question 10

To go from progesterone -> cortisol, what CYPS are needed

Answer 10

CYP11B1

CYP17

CYP21

these are types of CYTP450

Question 11

how many cyps in human genome

Answer 11

57

Question 12

Cortisol binds and activates what?

Answer 12

glucocorticoid receptor (GR)

Question 13

Why are glucorticoids inportant in infant respiratory distress syndrome

Answer 13

• During normal delivery, there is a burst of glucocorticoids that alters the bbs lung structure -> makes surfactant -> expands lungs so they can breath.
• In premature bbs, this process is defective and leads to infant. respiratory distress syndrome. This is prevented by giving mom glucocorticoids.

Question 14

aldoesterone binds and activates what receptor

Answer 14

mineralcorticoid receptor

Question 15

Patients with congenital adrenal hyperplasia present with what?

Answer 15

1. Hirutism- excessive body hair in M and W where it does not normally grow. F patients will have general oligomenorrhea, which is infrquent menstruation and infertility.

Question 16

The clinical severity of CAH depends on what?

Answer 16

the degree of deficiency in the enzyme that encodes steroidogenisis, causing excess or deficient production of sex steroids.

95% cases involve 21-alpha- hydroxylase. 5% involve 11B-hydroxylase.

Question 17

congential adrenal hyperplasia tx

Answer 17

hormone replacement therapy

Question 18

What are the genetics of CAH?

Answer 18

Autosomal recessive

Question 19

If a patient has CAH with a mutant 11B-hydroxylase (CYP____), what happens?

Answer 19

CYP11B1

1. Corticosterone precursors build up, causing an excess of androgen productions (M and F sex hormones),
2. accumulation of 17-alpha- hydroxyprogesterone
3. accumulation of 11-deoxycorticosterone.

Question 20

Pts with CAH d/t a mutant 11B-hydroxylase will have an increase in 11-deoxycorticosterone. This will cause what?

Answer 20

• 11-deoxycorticosterone is a mineralcorticoid AGO. It will act like aldosterone
• Cause HTN by promoting increase Na+ and H20 retention, decrease in plasma K+,.

Question 21

In patients with 11-B hydroxylase (Cyp11B1) deficiency, only. ________ and ______ would increase d/t this enzyme deficnecy. Of the two compounds, _________ has a higher affinity for MR to produce HTN.

Answer 21

• 11-deoxycorticosterone
• 11-deoxyxcortisol
• Of these two, 11-deoxycorticosterone has a higher affinity for MR to cause HTN.

Question 22

In patients with CAD d/t 21-alpha-hydroxylase deficiency,

what hormones accumulate abnormally?

Answer 22

1. Decreased cortisol synthesis
2. Decreased aldosterone synthesis -> salt wasting
3. High ACTH levels

In the blood, progesterone, 17alpha-hydroxypregenolone, 17alpha-hydroxyprogesterone.

Question 23

What are the steroid hormone blood transporter proteins?

where are they made?

Answer 23

1. CBG- corticosteroid binding globulin
2. SHBG- sex steroid binding globulin

both are made in the liver.

Question 24

__________ is the precursor to the following hormones: progesterne, aldosternoe, cortisol, testosterone and estradiol. Mutations in __________, prevent us from makeing these.

Answer 24

Pregnenolone

1. CYPs
2. HSDs
3. Lyases

Question 25

More rare forms of CAH are caused by, \_\_\_\_\_\_\_\_\_\_\_\_\_, the enzyme that is the **gateway to make sex steroid hormones.**

Answer 25

**CYP17A1 (17-alpha-hydroxylase, you will only have aldosterone production.**

Question 26

**Isolated _17,20-lyase_ deficiency (ILD)**, the gateway to make androgens and estrogen sex steroids, causes what?

Answer 26

* No sex steroids; normal levels of glucocorticoids and mineralcorticoids. * Does not result in adrenal hyperplasia or HTN.

Question 27

What occurs with ILD?

Answer 27

* **Males**: underdeveloped genital, intersex, pseuhermaphroditism * **Females**: reduced/no puberty, lack of secondary sex characteristics, child like appearance in adulthood.

Question 28

What converts progesterone -\> testosterone?

Answer 28

**17,20 lyase**

Question 29

What stimulates the formation of **estradoil** and **estrone**?

Answer 29

* Androstenedione -\> [+ FSH] stimulates aromatase in ovaries -\> estrone * Testosterone -\> [+FSH] stimualtes aromatse in ovaries -\> estradoil

Question 30

In F, what regulates the production of GnRH?

Answer 30

Progesterone inhibits GHR from the hypothalamus, as well as FSH and LH release from the pituitary.

Question 31

In M, what regulates the production of GnRH?

Answer 31

* _Testosterone_ **inhibits GnRH** * _Testosterone_ also **inhibits the release of LH** from the pituitary gland, * _Inhibin_ **inhibits the release of FSH**

Question 32

Vit D production happens in several different. tissue. What. are. these tissues?

Answer 32

**1. Skin** **2. liver** **3. kidney** **4. intestine**

Question 33

Cholecalciferol (vit D3) is obtained in 2 ways. What are they?

Answer 33

1. Diet 2. Skin

Question 34

\_\_\_\_\_\_\_\_ is formed exclusively. in the liver by the **_25-hyroxylase enzyme_** (CYP\_\_\_\_)

Answer 34

**_25-hydroxycholecalciferol_** is formed exclusively. in the liver by the **_25-hyroxylase enzyme_** (**_CYP2R1)_**.

Question 35

_Hydroxylation states_ of vit. D forms what?

Answer 35

**Cholecalciferol (D3)**