Regulation of Steroidogenesis

Steroidogenesis involves the conversion of cholesterol to glucocorticoids, mineralocorticoids, and sex steroids, which regulate development and physiology. Steroidogenesis is often discussed in a gland-specific fashion, but is better understood as a single process that is repeated in each gland with cell type-specific variations. Thus, the regulation of steroidogenesis occurs by regulating the transcription and post-translational modification of the steroidogenic enzymes and co-factors, in a tissue-specific fashion. Most steroidogenic enzymes are either hydroxysteroid dehydrogenases or cytochrome P450 enzymes; the activities of these enzymes are modulated by post-translational modifications and co-factors, especially electron-donating redox partners. The first and rate-limiting steroidogenic step is catalyzed by P450scc in all steroidogenic tissues, determining steroidogenic capacity; the qualitative regulation of steroidogenesis determining the class of steroid produced is principally mediated by P450c17. Understanding steroidogenesis permits understanding disorders of sexual differentiation, reproduction, fertility, hypertension, obesity, and physiologic homeostasis, and is essential for rational steroid therapies.