Sexually dimorphic expression of rat CYP3A9 and CYP3A18 genes is regulated by growth hormone

The cDNAs for two CYP3A genes were isolated from the livers of rats using an RT-PCR approach with CYP3A subfamily-specific primers. Sequence analysis revealed these cDNAs to be identical to CYP3A9, which had previously been isolated from rat brain and nasal epithelium and the recently described CYP3A18. The hepatic expression of both genes was sexually dimorphic. Thus CYP3A18 mRNA levels were 25-fold higher in male livers compared to females, while CYP3A9 showed a reverse pattern with 6-fold higher expression in the liver of females. Exposure of male rats to the female pattern of growth hormone secretion led to an increase in hepatic CYP3A9 mRNA expression and suppressed expression of CYP3A18. These findings indicate that the CYP3A subfamily in rats has both male- and female-specific isoforms which are regulated by growth hormone in a manner similar to some other sexually dimorphic cytochrome P450s.