Steroid Hormones

Question 1

5 classes of steroids (hormone they make)

Answer 1

P-GAME

1. progestin (progesterone)
2. glucocorticoids (cortisol)
3. androgens (DHT, testosterone dihydrotestosterone)
4. mineralcorticoids (aldo)
5. estrogen (estradiol 17β)

Question 2

Steroid hormones enter target cells and bind to ___

Answer 2

intracellular receptors, members of the nuclear hormone receptor family

Question 3

How are steroid hormones transported in the blood?

Answer 3

With a binding/transport protein–usually binding globulins made by liver

Question 4

location of CYP family

Answer 4

inner mitochondrial membrane and SER

Question 5

general action of CYP family

Answer 5

• usually add hydroxyl group

- CYP11A1 also has second function where adds ketone C=O

Question 6

mono-oxygenases requiring molecular oxygen and NADPH

Answer 6

CYP enzyme family

Question 7

3βHSD family location and action

Answer 7

• located in smooth ER
• catalyzes the flip of the double bone from carbons 5-6 (D5) to 4-5 (D4)
• all bioactive steroids must undergo this reaction

Question 8

17βHSD (hydroxysteroid dehydrogenase)

Answer 8

important for adnrogens and estrogens

• reduce keton group to hydroxyl
• located in SER

Question 9

Steroidogenic enzymes display what type of expression

Answer 9

cell type-specific

Question 10

steroidogenic cells can synthesize cholesterol from ___

Answer 10

acetate

Question 11

Steroidogenic cells can import cholesterol as ____ via ___ or as ___ via ____

Answer 11

LDL via LDLR mediated endocytosis

HDL via SR-B1

Question 12

Steroidogenic cells can store cholesterol as ____ using the enzyme ____ and release free cholesterol via _____

Answer 12

cholesterol esters using ACAT (acylaCoA:cholesterol acyl transferase)

free cholesterol via HSL

Question 13

All steroidogenic cells are able to catalyze the first two reactions common to steroidogenic pathways. What are these two steps catalyzed by?

Answer 13

• CYP11A1

- 3βHSD

Question 14

Since CYp11A1 is located on the ____, a specific transfer protein is required to get free cholesterol from the cytoplasm to this location. What is the major protein involved?

Answer 14

• inner mitochondrial membrane

- Steroidogenic Acute Regulatory Protein (StAR)

Question 15

Lipid congenital adrenal hyperplasia

Answer 15

mutation in StAR

Question 16

Type 1 3βHSD is found in _____ while Type II in ____

Answer 16

Type 1- skin and placenta

Type II- steroidogenic glands

Question 17

Hypothalamus-Pituitary-Adrenal Cortex Axis

Answer 17

Hypothalamus –> CRH –> corticotropes –> ACTH –> Adrenal Cortex –> Cortisol

CRH=corticotropin-releasing hormone
ACTH= adrenalcorticotropic hormone

Question 18

Production of steroid hormones that are not in endocrine axes (3)

Answer 18

• aldosterone
• placental steroid hormons
• neurosteroids

Question 19

Rapid response of ACTH

Answer 19

increase CE –> FC
-Tropic hormones increase their release of cholesterol from lipid droplets, transfer FC into mitochondria, increase StAR so that CYP11A1 can generate P5

Question 20

Medium response of ACTH

Answer 20

• increase steroidogenic enzymes
• increase synthesis of steroidogenic hormones
• increase synthesis of LDL-R and SR-B1

Question 21

Long term response

Answer 21

Increased growth of steroidogenic gland (hyperplasia and hypertrophy)

Question 22

When steroid hormones pass through the cell membrane, they can reside in the cytoplasm tethered to a _____ or may reside in the ____

Answer 22

• chaperone protein (HSP90)

- nucleus

Question 23

Steroid hormone-receptor complex binds to ____ and recruits ____

Answer 23

specific DNA sequences (often as a dimer) and recruits co-regulatory proteins

can increase/decrease transcription of neighboring gene, altering chromatin structure

Question 24

about 2/3 of newly diagnosed invasive breast cancer express ____ and are dependent on ____ for their growth

Answer 24

estrogen receptor a (ERa)

estradiol

Question 25

If the tumor is ER-positive, it will likely respond to the mixed ER agonist/antagonist, _____

Answer 25

tamoxifen (agonist/antagonist for the receptor)

it binds, and thus prevents estrogen from binding to the receptor, hence breast cancer cell growth is blocked