Ontogenic Development of Steroid 16alpha-Hydroxylase as a Tool for the Study of the Multiplicity of Cytochrome P-450

Abstract

Activities of progesterone, testosterone, pregnenolone and dehydroepiandrosterone 16.alpha.-hydroxylase are undetectable in the fetal rat liver. During the neonatal period, the 4 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 4 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. In the adult rat liver, steroid 16.alpha.-hydroxylase is supported by 2 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 2 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 2 forms occurs during puberty and is correlated with the sexual differentiation of the steroid 16.alpha.-hydroxylase activities. 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 2 rat liver monooxygenases: steroid 16.alpha.-hydroxylase and aryl hydrocarbon hydroxylase. 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. 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.