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ADRENAL STEROIDOGENESIS

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Cholesterol

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Cholesterol is an essential component of many cellular and developmental processes and is the precursor for all adrenal and gonadal steroid hormones, bile acids, and neurosteroids. The cholesterol molecule (27 carbons) is synthesized from lanosterol through a series of approximately 30 enzymatic reactions (see Chapter 23).

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Adrenals can synthesize cholesterol de novo from acetate and coenzyme A, but most cholesterol is of dietary origin, provided by plasma low-density lipoproteins (LDLs). Two families of enzymes play a leading role in the conversion of cholesterol to adrenal steroid hormones: cytochrome P450s and hydroxysteroid dehydrogenases.

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Steroidogenic Enzymes

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Cytochrome P450s
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Most of the enzymes involved in the synthesis of adrenal steroids belong to the cytochrome P450 enzyme family, which are membrane-bound proteins associated with either mitochondria or the endoplasmic reticulum (microsomal). P450 enzymes function as monooxygenases using reduced nicotinamide adenine dinucleotide phosphate (NADPH) as the electron donor for the reduction of the molecular oxygen.1

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The mitochondrial P450scc enzyme and P450c11 isozymes, P450c11β and P450c11AS, respectively, receive electrons from the NADPH through a sequential electron shuttle transfer involving two proteins, adrenodoxin reductase (a flavoprotein)2 and adrenodoxin (a non heme iron–sulfur protein).3 The microsomal P450c17, P450c21, P450arom enzymes, receive electrons from the reduced form of NADPH using only one membrane-bound flavoprotein, P450 oxidoreductase (POR), to transfer the electrons from NADPH to POR to P450 enzymes.

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Hydroxysteroid Dehydrogenases
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The hydroxysteroid dehydrogenases, which include 3β-HSD and 17β-HSD isozymes, are involved in the reduction and oxidation of adrenal and gonadal steroids in the presence of NAD+/NADP+ or their reducing equivalents as cofactors (Table 29-1).

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Table Graphic Jump Location
TABLE 29-1Steroidogenic Enzymes

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