Sequence and regulation of two growth-hormone-controlled, sex-specific isozymes of cytochrome P-450 in rat liver, P-450(15)beta and P-450(16)alpha.

Full length cDNA clones for the sexually differentiated rat liver cytochrome P-450 isozymes 15 beta and 16 alpha have been isolated and sequenced. The deduced amino acid sequence of P-450(15)beta is 66% homologous to that of P-450(16)alpha. Furthermore, either of these two cytochromes has a homology of about 50% with the major phenobarbital inducible form, cytochrome P-450b, while the homology with the major carcinogen inducible form, cytochrome P-450c, is less than 30%. Also, the homology of these two sex-dependent cytochromes with the developmentally regulated cytochrome P-450 isozymes f and PB-1 is about 70%. Therefore, it is concluded that P-450 isozymes 15 beta, 16 alpha, f, and PB-1 represent a subfamily within the phenobarbital related cytochrome P-450 gene family. Growth hormone is known to be a major determinant for expression of P-450(15)beta and P-450(16)alpha and the time course of this induction was studied at the pretranslational level. Continuous infusion of GH to hypophysectomized male rats caused an induction of P-450(15)beta mRNA after 6 days of treatment while intermittent injections had no effect during that time course. The opposite was found to be the case for P-450(16)alpha mRNA where no effect was observed following continuous administration of GH, whereas intermittent injections caused an induction after 2 days of treatment.