L10 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 receptors.
• Low in concentration; high affinity receptor
• Minutes to hours

Question 2

Describe the hormones that interact with intracellular receptors and how they interact

Answer 2

• Hydrophobic hormones
• Bind to receptors inside of cell
• Receptor brings hormone to nucleus of cell

Question 3

Describe the hormones that interact with cell-surface receptors and how they interact

Answer 3

• Extracellular hydrophilic hormones, neurotransmitters, growth factors
• Bind to receptors on cell surface
• Stimulate second messengers inside of cell

Question 4

Describe the common features in the structures and the mechanism of steroid hormone receptors

Answer 4

• Bind to steroid hormones & regulate transcriptions of a specific set of genes
• Belong to the “nuclear receptor” family
• Contain a DNA binding domain & hormone binding domain

Question 5

Identify the major organs responsible for steroid synthesis

Answer 5

Ovaries, Testes, Adrenal glands

Question 6

Describe 17α-hydroxylase deficiency

Answer 6

Causes an overproduction of mineralocorticoids (aldosterone) & deficiency of corticosteroids & sex hormones

Question 7

What reactions are prevented due to 17α-hydroxylase deficiency?

Answer 7

Pregnenolone → intermediate → Cortisol

Progesterone → Cortisol

Question 8

What are the symptoms of 17α-hydroxylase deficiency?

Answer 8

• Hypocortisolism → enlargement of adrenal glands (no negative feedback loop)
• Ambiguous genitalia
• Hyperaldosteronism → hypertension

Question 9

Describe 21-hydroxylase deficiency

Answer 9

Overproduction of sex hormones & underproduction of aldosterone & cortisol

Question 10

What reactions are prevented due to 21-hydroxylase deficiency?

Answer 10

Progesterone → intermediate → aldosterone

Progesterone → intermediate → cortisol

Question 11

What are the symptoms of 21-hydroxylase deficiency?

Answer 11

• Hypocortisolism → enlargement of the adrenal glands
• Hypoaldosteronism → hyponatremia; can be life-threatening in infants
• Premature androgen exposure causing…
  Ambiguous genitalia in female
  Hirsutism
  Early epiphyseal closure → short stature

Question 12

Name the drugs used to regulate steroid synthesis

Answer 12

Aminoglutethimide (Cytadren)

Ketoconazole (Nizoral)

Question 13

Describe the action of Aminoglutethimide

Answer 13

Inhibits aromatase & P450scc

Question 14

Describe the action of Cytadren

Answer 14

Inhibits aromatase & P450scc

Question 15

Describe the action of Ketoconazole

Answer 15

Inhibits P450scc, 17a-hydroxylase & 11b-hydroxylase

Question 16

Describe the action of Nizoral

Answer 16

Inhibits P450scc, 17a-hydroxylase & 11b-hydroxylase

Question 17

Describe the clinical use of Aminoglutethimide

Answer 17

Used to block steroid production in some hormone-dependent tumors (breast, prostate)

Question 18

Describe the clinical use of Cytadren

Answer 18

Used to block steroid production in some hormone-dependent tumors (breast, prostate)

Question 19

Describe the clinical use of Ketoconazole

Answer 19

Can treat hyperglucocorticoid states (Cushing’s syndrome)

antifungal @ lower conc. (block the synthesis of ergosterol

Question 20

Describe the clinical use of Nizoral

Answer 20

Can treat hyperglucocorticoid states (Cushing’s syndrome)

antifungal @ lower conc. (block the synthesis of ergosterol

Question 21

What are some problems with Ketoconazole?

Answer 21

May cause toxic side effects

Question 22

What are some problems with Nizoral?

Answer 22

May cause toxic side effects