Lecture 5. Steroid Hormone Metabolism

Question 1

Name the 5 classes of steroid hormones

Answer 1

Glucocorticoids - cortisol
mineralocorticoids 
androgens 
estrogens
progestins

Question 2

Indicate the steroid hormones synthesized by the different adrenal cortex layers, and the role of ACTH in their release

Answer 2

.Z. Glomerulosa: aldosterone
Z. Fasciculata: cortisol + androgens
Z. Reticularis: androgens

The role of ACTH:

• ACTH acts ONLY on the Z. Fasciculata & Z. Reticularis
• ACTH stimulates Z. Fasciculata to release cortisol
• ACTH stimulates Z Reticularis to release Androgens

Question 3

Outline the synthesis and the metabolic actions of aldosterone. Indicate the role of angiotensin.

Answer 3

Synthesis:
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Metabolic Action:

• Primary effect on kidney tubules
• stimulates Sodium re-uptake, potassium secretion
• increases water reabsoprtion, increased blood pressure

Role of Angiotensin:

• the Z. Glomerulosa has receptors for Angiotensin II, which is formed at decreased blood pressure and stimulates the synthesis of aldosterone

Question 4

Review the synthesis and the metabolic actions of cortisol

Answer 4

Synthesis:
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Metabolic Action:

• on the liver: gluconeogenesis
• on adipose tissue: decrease TAG stores & increase free fatty acids
• on muscle tissue: degradation of muscle proteins
• modulation of inflammatory response (Inhibit PLA2 and eicosanoid synthesis)

Question 5

Indicate the synthesis of DHEA and androestenedione in adrenal cortex. Describe the synthesis of testosterone and estrogen from DHEA and androstenedione in peripheral tissues.

Answer 5

Synthesis of DHEA:
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Synthesis of testosterone/estrogen:

Question 6

Discuss steroid hormone synthesis related to StAR and desmolase (CYP 11A). Outline steroid synthesis in the adrenal cortex.

Answer 6

StAR function:

• StAR is responsible for transport of cytosolic free cholesterol into the mitochondria
• StAR is activated by ACTh released from the pituitary (via PKA mechanism)

Desmolase (CYP11A) function:

• Desmolase is involved in the RATE LIMITING step of steroid hormone synthesis
• in the mitochondria, Desmolase is responsible for cleaving the side chain of free cholesterol (27 carbon chain) to Pregnenolone (21 carbon chain)

Steroid synthesis:
***

Question 7

Discuss congenital adrenal hyperplasias (CAH) and describe clinical features and biochemical basis of manifestations in patients with deficiencies of 3-hydroxysteroid DH, CYP21, CYP11B, and CYP17. Differentiate between the various enzyme deficiencies resulting in CAH

Answer 7

CAH: an autosomal recessive disorder characterized by decreased synthesis of cortisol.

There are several enzyme deficiencies that result in CAH symptoms:

1. Deficiency of 3-hydroxysteroid DH
   
   • No formation of progesterone
     - Significantly decreased aldosterone and cortisol synthesis
     - increased salt excretion in the urine
     Key symptoms: Ambiguous Genitalia (DHEA is stimulated, but there is not sufficient levels for normal genitalia development)
2. Deficiency of CYP 21
   - the most common enzyme deficiency in CAH
   - results in decreased synthesis of deoxycorticosterone, aldosterone & cortisol
   - results in an increase in androgen synthesis
   Key symptoms: masculinization, HYPOtension, salt crisis
3. Deficiency of CYP11B
   - decreased synthesis of cortisol and aldosterone
   - BUT increase in synthesis of deoxycorticosterone

Key symptoms: mild HYPERtension, masculinzation

4. Deficiency of CYP17
   - decreased synthesis of DHEA, androstenedione, & cortisol
   - increased synthesis of aldosterone

Key symptoms: HYPERtension, female like genitalia in males and females.

Question 8

Describe the synthesis of testosterone in testes and of estradiol in ovaries. Discuss the functions of 5-alpha hydroxylase and aromatase (CYP13).

Answer 8

Synthesis of Testosterone:
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Function of 5-alpha hydroxylase:
-

Question 9

Indicate the hormone abnormality in: Cushing’s syndrome and Addison’s disease.

Answer 9

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Question 10

Indicate the biochemical basis for the occurence of hyperglycemia in Cushing’s Syndrome.

Answer 10

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