ABSTRACT
P450c17 (CYP17) catalyzes both 17α-hydroxylase and 17,20-lyase activities, and hence is the qualitative regulator of human steroidogenesis, determining which class of steroids will be produced. The two activities are differentially regulated developmentally and in a tissuespecific fashion. Biochemical, computational, and mutagenesis studies all indicate that the ratio of lyase to hydroxylase activity is regulated by the availability of the electron donor, NADPH-cytochrome P450 oxidoreductase, and by the ability of CYP17 to interact with this reductase in a productive fashion. Three factors can increase the lyase:hydroxylase ratio: (1) increasing the molar abundance of P450 oxidoreductase; (2) increasing the abundance of cytochrome b5, which allosterically facilitates interaction between P450c17 and the oxidoreductase; and (3) serine/threonine phosphorylation of CYP17 itself. These multiple mechanisms permit the fine control of adrenal and gonadal C19 steroid production.
