E2 L1: Biosynthesis of Steroid Hormones

Question 1

Explain the characteristics of endocrine signaling:

Answer 1

-Travels fairly far through the blood to a target organ expressing receptor
-Low in concentration; high affinity receptor
-Minutes to hours

Question 2

Intracellular signaling

Answer 2

Transcription factors; signaling molecule must penetrate cell;
HAS TO BE HDYROPHOBIC W/NO CHARGES
penetrate->bind to intracellular receptor

Question 3

Cell surface signaling

Answer 3

Hydrophilic/charged - Signal molecule binds->receptor activates->second messenger-> concentration goes up inside the cell

Question 4

Intracell signaling example

Answer 4

Steroid hormones

Question 5

Cell surface signaling example

Answer 5

GPCRs

Question 6

Common features of steroid hormones

Answer 6

-Synthesized from cholesterol
-Planar, rigid, and hydrophobic = TIGHT BINDING TO RECEPTORS
-Exist in very low concentrations in body (0.1 - 10 nM)
-Bound to serum carrier proteins

Question 7

Steroid hormones: Mode of action

Answer 7

Free hormones diffuse through cell membrane and bind to a specific steroid hormone receptor (endocrine)
-Regulate transcription of a specific set of genes

Question 8

Steroid receptors that bind steroid hormones and regulate transcriptions of specific set of genes:

Answer 8

Estrogen receptor
Androgen receptor
Corticosteroid receptor
Aldosterone receptor
Progesterone receptor

Question 9

Steroid receptors that belong to nuclear receptor family:

Answer 9

Steroid receptors
Thyroid hormone receptor
Retinoic acid receptor
Vitamin D receptor

Question 10

Major organs responsible for steroid synthesis:

Answer 10

Adrenal cortex, gonads, and placenta

Question 11

17a-hydroxylase deficiency:

Answer 11

Rare form of congenital adrenal hyperplasia (5%)
Caused by mutations in CYP17A1, which has both 17a-hydroxylase and 17,20-lyase activities
Overproduction of mineralocorticoids and deficiency of corticosteroids and sex hormones
Symptoms:
Hypercortisolism-> enlargement of the adrenal glands
Ambiguous genitalia
Hyperaldosteronism-> HTN

Question 12

21-hydroxylase deficiency:

Answer 12

Major form of congenital adrenal hyperplasia (95%)
Mutations in CYP21A2, which functions as a 21-hydroxylase
Symptoms:
Hypocortisolism-> enlargement of adrenal glands
Hypoaldosteronism-> hyponatremia; can be life-threatening in infants
-Premature androgen exposure:
Ambiguous genitalia in female
Hirsutism
Early epiphyseal closure (short stature)

Question 13

Drugs used to regulate steroid synthesis:

Answer 13

Aminoglutethimide (Cytadren)
Ketoconazole (Nizoral)

Question 14

Aminoglutehimide:

Answer 14

Inhibits aromatase and P450scc
Used to block steroid production in some hormone dependent tumors (breast, prostate)

Question 15

Ketoconazole:

Answer 15

Antifungal at low conc (blocks synthesis of ergosterol)
Inhibits P450sc, 17a-hydroxylase, and 11B hydroxylase
Can treat hyper glucocorticoid states (Cushing’s syndrome)
May cause toxic side effects