Ontogenic development of steroid 16 alpha-hydroxylase as a tool for the study of the multiplicity of cytochrome P-450

Abstract

1. Activities of progesterone, testosterone, pregnenolone and dehydroepiandrosterone 16 alpha-hydroxylase are undetectable in the fetal rat liver. During the neonatal period, the four enzymic activities increase in parallel to the concentration of cytochrome P-450. Until puberty, they develop similarly in male and female rat livers. From the 40th to the 55th day, the four steroid 16 alpha-hydroxylase activities increase rapidly in the male rat liver. The sexual differentiation of the steroid 16 alpha-hydroxylation observed in adult male and female rats takes place around the 55th day. 2. In the adult rat liver, steroid 16 alpha-hydroxylase is supported by two forms of cytochrome P-450 (form I and form II), which differ in their relative affinities for the various steroid substrates, and by their relative proportions in male and female rat livers. These two forms of cytochrome P-450 are also present in the young male and female rat livers, but are roughly equal in proportion. The transition from the immature to the adult repartition of the two forms occurs during puberty and is correlated with the sexual differentiation of the steroid 16 alpha-hydroxylase activities. 3. During the critical phases of the rat ontogenic development, the in vitro interactions between benzo[a]pyrene and steroids were compared at the level of two rat liver monooxygenases: steroid 16 alpha-hydroxylase and aryl hydrocarbon hydroxylase. (a) In the immature male and female rat livers, progesterone 16 alpha-hydroxylase, and to a lesser extent, pregnenolone 16 alpha-hydroxylase are inhibited by benzo[a]pyrene. Progesterone 16 alpha-hydroxylase is also inhibited by metyrapone. (b) In the young rat, aryl hydrocarbon hydroxylase cannot be inhibited by steroids and appears to be supported by a single form of cytochrome P-450. The transition from the immature to the adult situation occurs around the 40th day.