Biosynthesis of Steroid Hormones

Question 1

Describe the structural characteristics of steroids

Answer 1

-Synthesized from cholesterol.

-Tight binding to receptor due to:
Planar( four rings are connect)
Rigid (cannot change conformation)
Hydrophobic (only 1 hydroxyl group)

• C-1 to C-10 has 2 ring
• C-11 to C-17 has 2 ring
• C-3 has an hydroxyl group
• C-18 and C-19 has a methyl group
• C-20 to C-21

-Exist in very low concentrations in the body (0.1 – 10 nM).

• Bound to serum carrier proteins.
• Share the common mode of action:
• Free hormones diffuse through the cell membrane and bind to a specific steroid hormone receptor.
• Regulate transcription of a specific set of genes
• Each steroid hormone have a different set of genes they activate

Question 2

Identify and distinguish the structures of cortisol, aldosterone, progesterone, testosterone, and 17β-estradiol.

Answer 2

SEE SLIDE 5

• Cortisol: C-11 hydroxyl group and C-17 hydroxyl group
• Aldosterone: C-11 hydroxyl group and No C-17 hydroxyl group
• Progesterone: 21 hydroxyl group and esther group
• Testosterone: ketone structure, C-17 hydroxyl group and 19 carbon
• 17β-estradiol: aromatic ring, 2 hydroxyl group, and 18 carbon

Question 3

Order the intermediates according to their appearance in the steroid synthesis pathways.

Answer 3

SEE SLIDE 7

Question 4

Identify the major organs in which each step of steroid synthesis occurs.

Answer 4

-Dihydroepi-androsterone (DHEA)- INTERMEDIATE- use to make sex hormone

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Question 5

Identify the major organs in which each step of steroid synthesis occurs.

Answer 5

-The Adrenal Gland

Question 6

Describe the consequence of a genetic disorder in steroid synthesis on the level of each steroid hormones.

Answer 6

• 17α-hydroxylase deficiency
• Rare form of congenital adrenal hyperplasia (5%)
• Caused by mutations in CYP17A1, which has both 17α-hydroxylase and 17,20-lyase activities.
• Overproduction of mineralocorticoids and deficiency of corticosteroids and sex hormones.
• Symptoms:
• Hypocortisolism : enlargement of the adrenal glands
• Ambiguous genitalia:
• Hyperaldosteronism: hypertension
• 21-hydroxylase deficiency
• Major form of congenital adrenal hyperplasia (95%)
• Mutations in CYP21A2, which functions as 21-hydroxylase
• Symptoms
• Hypocortisolism  enlargement of the adrenal glands
• Hypoaldosteronism  hyponatremia; can be life-threatening in infants
• Premature androgen exposure
• Ambiguous genitalia in female
• Hirsutism
• Early epiphyseal closure  short stature