Mediation of the Hormonal Stimulation of Steroidogenesis by the Polypeptide Diazepam Binding Inhibitor

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).