Characterization and regulation of sex-specific mouse steroid hydroxylase genes

Abstract

We characterized the genes of the male-specific mouse steroid 16α-hydroxylase (C-P-45016α) and the female-specific mouse steroid 15α-hydroxylase (P-45015α) within two distinct gene families. In spite of the high structural identities within each family, the expression of the hydroxylase genes is uniquely regulated. Moreover, the other family members encode the P-450s which are structurally very similar to the hydroxylases but are not able to catalyze steroid hydroxylase activities. For example, only a single amino acid substitution creates steroid 15α-hydroxylase activity in another family-member P-450coh, which catalyzes coumarin 7-hydroxylase but little steroid hydroxylase activity. It appears, therefore, that the mouse P-450 gene families evolved through gene duplication and selective mutation to create new P-450s structurally as well as to establish novel regulatory elements for the gene expressions.Key words: cytochrome P-450, steroid hydroxylase, site-directed mutagenesis, evolution, gene regulation.