Sequence and Regulation of Two Growth‐hormone‐contn Sex‐specific Isozymes of Cytochrome P‐450 in Rat Liver, P‐450_15β and P‐450_16α

Full length cDNA clones for the sexually differentiated rat liver cytochrome P450 isozymes 15β and 16α have been isolated and sequenced. The deduced amino acid sequence of P450(15β) is 66% homologous to that of P-450(16α). Furthermore, either of these two cytochromes has a homology of about 50% with the major phenobarbital inducible form, cytochrome P-450(b), while the homology with the major carcinogen inducible form, cytochrome P-450(c), 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 15β, 16α, 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 P450(15β) and P-450(16α) 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 P450(15β) 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(16α) mRNA where no effect was observed following continuous administration of GH, whereas intermittent injections caused an induction after 2 days of treatment.