The regulation of steroidogenesis by 17α-hydroxylase/17, 20-lyase (P450c17)

Abstract

Cytochrome P450c17 (P450c17) catalyzes 17α-hydroxylation and 17, 20-lyase reactions. This enzyme plays a key role in determination of the balance between glucocorticoids and steroid sex hormones. In this review, we discuss recent progress in the studies of both transcriptional regulation of CYP17 encoding P450c17 and enzymatic regulation of P450c17. Several transcription factors involved in cAMP-dependent transcription of the gene have been isolated and identified to be members of the atypical homeodomain “TALE” superfamily containing Pbx, Meis, Pknox and TGIF families. The studies of enzymatic regulation of P450c17 suggest that cytochrome b₅ (b₅), a heme protein, may switch the reaction of P450c17 by enhancing the 17, 20-lyase activity to increase the level of plasma C19 steroids. The importance of b₅ in the synthesis of C19 steroids has also been shown in a clinical study reporting that the external genitalia was abnormal in a patient having a defect in b₅. Therefore, this enhancement by b₅ on the lyase activity of P450c17 may beessential to normal sexual differentiation in humans and also important in control of an optimal balance between sex steroid hormones and glucocorticoids. In addition, the age-dependent expression of P450c17 in immature rat livers is also discussed.