HORMONAL-REGULATION OF MICROSOMAL CYTOCHROME-P450 2C11 IN RAT-LIVER AND KIDNEY

The current study was conducted to investigate hormonal regulation of cytochrome P450 2C11 (CYP2C11) in rat liver and kidney of adult male r ats, In two experiments, hypophysectomy (Hx) resulted in decreased (P < .05) hepatic CYP2C11 apoprotein and mRNA levels. Growth hormone (GH) replacement of Hx rats prevented the decline in hepatic CYP2C11 apopr otein and mRNA levels, whereas, subcutaneous injection of testosterone had no effect, Rat pituitary extract is equally effective in intact o r castrated Hx rats in preventing the decline in hepatic CYP2C11 apopr otein and mRNA levels. Specific neutralization of rat GH by sheep anti -rat GH serum reduced (P < .05) serum IGF-I concentrations, hepatic CY P2C11 apoprotein and mRNA levels. Hx of male rat resulted in decreased (P < .05) renal CYP2C11 apoprotein and mRNA levels, and treatment wit h GH failed to prevent these effects; however, supplementation of Hx r ats with testosterone or rat pituitary extract prevented the Hx-induce d decrease of renal CYP2C11 apoprotein and mRNA levels, and the effect s of rat pituitary extract occurred only in intact rats. Neutralizatio n of rat GH by anti-rGH significantly reduced (P < .05) CYP2C11 mRNA l evels and serum T concentrations but not serum LX concentrations. Thes e results indicate that although hepatic CYP2C11 is regulated by GH, r at renal CYP2C11 is regulated primarily by gonadal steroids.