Lecture 5. Steroid Hormone Metabolism Flashcards Preview

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Flashcards in Lecture 5. Steroid Hormone Metabolism Deck (10):
1

Name the 5 classes of steroid hormones

Glucocorticoids - cortisol
mineralocorticoids
androgens
estrogens
progestins

2

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

.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

3

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

Synthesis:
***


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

4

Review the synthesis and the metabolic actions of cortisol

Synthesis:
***

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)

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.

Synthesis of DHEA:
***

Synthesis of testosterone/estrogen:

***

6

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

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:
***

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

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.

8

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

Synthesis of Testosterone:
***


Function of 5-alpha hydroxylase:
-

9

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

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10

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

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