Steroid Biosynthesis

Trophic hormone regulation of steroid synthesis can be thought as being either "acute"—occurring within minutes and results in the rapid synthesis of steroids, or "chronic"—occurring over a long period of time and resulting in continued steroid production. The primary point of control in the acute stimulation of steroidogenesis by hormones involves the first step in this biosynthetic pathway, where the substrate cholesterol is converted to pregnenolone (PREG) by the cholesterol side-chain cleavage cytochrome P-450 enzyme (P-450scc) and auxiliary electron-transferring proteins, localized on inner mitochondrial membranes (44-47). More detailed studies have shown that the reaction catalyzed by P-450scc is not the rate-limiting step in the synthesis of steroid hormones, but rather it is the transport of the precursor—cholesterol—from intracellular sources to the inner mitochondrial membrane and the subsequent loading of cholesterol in the P450scc active site (44-47). This hormone-dependent transport mechanism was shown to be mediated by cyclic adenosine monophosphate (cAMP), to be regulated by a cytoplasmic protein, and to be localized in the mitochondrion, where it regulates the intramitochondrial transport of cholesterol (44-47). Although a number of molecules have been proposed as potential candidates mediating this intramitochondrial cholesterol transfer (46,47), no clear evidence has been presented on the identity of this mechanism. During the last decade, however, a new cholesterol-transport mechanism was identified and characterized as mediating the acute stimulation of steroidogenesis by hormones, the PBR protein (6).

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