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Steroid Hormone Biosynthesis Reactions
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Steroid Hormone Biosynthesis Reactions - 09-11-2006, 01:58 AM

The particular steroid hormone class synthesized by a given cell type depends upon its complement of peptide hormone receptors, its response to peptide hormone stimulation and its genetically expressed complement of enzymes. The following indicates which peptide hormone is responsible for stimulating the synthesis of which steroid hormone:

• Luteinizing Hormone (LH):
 progesterone and testosterone
• Adrenocorticotropic hormone (ACTH):
 cortisol
• Follicle Stimulating Hormone (FSH):
 estradiol
• Angiotensin II/III:
 aldosterone

The first reaction in converting cholesterol to C18, C19 and C21 steroids involves the cleavage of a 6-carbon group from cholesterol and is the principal committing, regulated, and rate-limiting step in steroid biosynthesis. The enzyme system that catalyzes the cleavage reaction is known as P450-linked side chain cleaving enzyme (P450ssc), or desmolase, and is found in the mitochondria of steroid-producing cells, but not in significant quantities in other cells.

Mitochondrial desmolase is a complex enzyme system consisting of cytochrome P450, and adrenadoxin (a P450 reductant). The activity of each of these components is increased by 2 principal cAMP- and PKA-dependent processes. First, cAMP stimulates PKA, leading to the phosphorylation of a cholesteryl-ester esterase and generating increased concentrations of cholesterol, the substrate for desmolase. Second, long-term regulation is effected at the level the gene for desmolase. This gene contains a cAMP regulatory element (CRE) that binds cAMP and increases the level of desmolase RNA transcription, thereby leading to increased levels of the enzyme. Finally, cholesterol is a negative feedback regulator of HMG CoA reductase activity (see regulation of cholesterol synthesis). Thus, when cytosolic cholesterol is depleted, de novo cholesterol synthesis is stimulated by freeing HMG CoA reductase of its feedback constraints. Subsequent to desmolase activity, pregnenolone moves to the cytosol, where further processing depends on the cell (tissue) under consideration.

The various hydroxylases involved in the synthesis of the steroid hormones have a nomenclature that indicates the site of hydroxylation (e.g. 17a-hydroxylase introduces a hydroxyl group to carbon 17). These hydroxylase enzymes are members of the cytochrome P450 class of enzymes and as such also have a nomenclature indicative of the site of hydroxylation in addition to being identified as P450 class enzymes (e.g. the 17a-hydroxylase is also identified as P450c17).


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