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Trophic hormone regulation of steroid synthesis can be thought of as being either acute, occurring within minutes and resulting 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 cholesterol is converted to pregnenolone by the cholesterol side-chain cleavage cytochrome P-450 (P-450scc) enzyme and auxiliary electron transferring proteins, localized on the inner mitochondrial membranes (1–4). 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 the transport of the precursor, cholesterol, from intracellular sources to the inner mitochondrial membrane and the subsequent loading of cholesterol in the P-450scc active site (1–4). This hormone-dependent transport mechanism was shown to be mediated by adenosine 3′:5′-cyclic monophosphate (cAMP), to be regulated by a cytoplasmic protein, and to be localized in the mitochondrion where it regulates the intramitochondrial transport of cholesterol (1–4).

Eukaryotic steroid hormones, derived from cholesterol, are responsible for the maintenance of the organism’s homeostasis, adaptability to the environment, and developmental and reproductive functions. The mechanisms by which pituitary trophic hormones, such as adrenocorticotropin and luteinizing hormone (LH), act on their respective target organs, adrenal and gonads, to stimulate steroidogenesis have been under extensive investigation during the last 40 years (1–5). Both hormones bind to cell surface receptors that activate adenylyl cyclase that then initiates a complex series of events in which cAMP-dependent protein kinase and cholesterol esterase are involved, ultimately increasing delivery of cholesterol to the cytochrome P450 side-chain cleavage enzyme (P450scc). Cholesterol is liberated from extramitochondrial stores, transported to mitochondria, incorporated into the outer mitochondrial membrane, and finally delivered to the inner mitochondrial membrane where it is converted to pregnenolone by P450scc and auxiliary electron-transferring proteins (1–5).