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Steroid hormones share a common characteristic in that, regardless of the tissue of origin or the final steroid synthesized, they all arise from a common precursor substrate, cholesterol. Thus the biosynthesis of all steroids begins with the cleavage of cholesterol to form the first steroid synthesized, pregnenolone. This reaction is catalyzed by the cytochrome P450 side chain cleavage enzyme (P450scc), which is located on the matrix side of the inner mitochondrial membrane (Simpson and Boyd 1966, 1967; Farkash et al. 1986). Once formed, pregnenolone can be converted within the mitochondria to progesterone by a mitochondrial form of 3s-hydroxysteroid dehydrogenase (3s-HSD; Cherradi et al. 1997). Exiting the mitochondria, progesterone undergoes further metabolism by microsomal steroid dehydrogenases and cytochrome P450 steroid hydroxylases to form tissue specific steroids. |
