Question

Explain the steroid hormone synthesis beginning with cholesterol to mineralocorticoid and glucocorticoid.

Hint:

The synthesis of cortisol and aldosterone from cholesterol involves multiple enzymatic steps, with different enzymes catalyzing distinct reactions in the adrenal cortex.

Answer 1

The synthesis of steroid hormones begins with cholesterol, which is the precursor for all steroid hormones. This process primarily occurs in the adrenal glands, gonads, and the placenta.
Step 1: Conversion of Cholesterol to Pregnenolone:
Cholesterol, which is derived from dietary sources or synthesized in the liver, is first converted into pregnenolone in the mitochondria. This is the rate-limiting step in steroid hormone biosynthesis and is catalyzed by the enzyme CYP11A1 (side-chain cleavage enzyme).
Step 2: Pregnenolone to Progesterone:
Pregnenolone is converted into progesterone by the enzyme 3β-hydroxysteroid dehydrogenase (3β-HSD). Progesterone is a precursor for both mineralocorticoids and glucocorticoids.
Step 3: Glucocorticoid Synthesis (Cortisol):
From progesterone, the next steps occur primarily in the zona fasciculata of the adrenal cortex. The enzyme CYP17A1 converts progesterone to 17-hydroxyprogesterone, which is further converted to 11-deoxycortisol by 21-hydroxylase. Finally, 11-deoxycortisol is converted into cortisol (a glucocorticoid) by 11β-hydroxylase.
Step 4: Mineralocorticoid Synthesis (Aldosterone):
In the zona glomerulosa of the adrenal cortex, progesterone is first converted into 11-deoxycorticosterone (DOC), which is then converted to aldosterone by the enzyme 21-hydroxylase. Aldosterone is a mineralocorticoid that regulates sodium and water balance.