Flashcards in Lecture 5. Steroid Hormone Metabolism Deck (10):
Name the 5 classes of steroid hormones
Glucocorticoids - cortisol
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
Outline the synthesis and the metabolic actions of aldosterone. Indicate the role of angiotensin.
- 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
Review the synthesis and the metabolic actions of cortisol
- 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)
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:
Discuss steroid hormone synthesis related to StAR and desmolase (CYP 11A). Outline steroid synthesis in the adrenal cortex.
- 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)
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.
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:
Indicate the hormone abnormality in: Cushing's syndrome and Addison's disease.