Vol. 283, Issue 3, 1486-1494, 1997

Hormonal Regulation of Microsomal Cytochrome P450 2C11 in Rat Liver and Kidney¹

Gen-Fu Chen, Martin J. J. Ronis, Paul E. Thomas, David J. Flint and Thomas M. Badger

Department of Pediatrics (G.-F.C., M.J.J.R., T.M.B.), University of Arkansas for Medical Sciences, Arkansas Children's Hospital Research Institute, Little Rock, Arkansas; Rutgers College of Pharmacy (P.E.T.), Rutgers, New Jersey; and Hannah Research Institute (D.J.F.), Ayr KA6 5HL, Scotland

The current study was conducted to investigate hormonal regulation of cytochrome P450 2C11 (CYP2C11) in rat liver and kidney of adult male rats. 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 apoprotein and mRNA levels, whereas, subcutaneous injection of testosterone had no effect. Rat pituitary extract is equally effective in intact or castrated Hx rats in preventing the decline in hepatic CYP2C11 apoprotein and mRNA levels. Specific neutralization of rat GH by sheep anti-rat GH serum reduced (P < .05) serum IGF-I concentrations, hepatic CYP2C11 apoprotein and mRNA levels. Hx of male rat resulted in decreased (P < .05) renal CYP2C11 apoprotein and mRNA levels, and treatment with GH failed to prevent these effects; however, supplementation of Hx rats with testosterone or rat pituitary extract prevented the Hx-induced decrease of renal CYP2C11 apoprotein and mRNA levels, and the effects of rat pituitary extract occurred only in intact rats. Neutralization of rat GH by anti-rGH significantly reduced (P < .05) CYP2C11 mRNA levels and serum T concentrations but not serum LH concentrations. These results indicate that although hepatic CYP2C11 is regulated by GH, rat renal CYP2C11 is regulated primarily by gonadal steroids.