INSULIN-LIKE-GROWTH-FACTOR-1 (IGF-I) EFFECTS ON SEX-SPECIFIC CYTOCHROME-P450 ENZYMES IN NORMAL AND HYPOPHYSECTOMIZED MALE RATS

The role of growth hormone (GH) in the regulation of the sex-different iated rat cytochrome P450 (CYP) enzymes has been extensively studied. However, little is known about the involvement of insulin-like growth factor I (IGF-I) as a mediator in this regulation. We wanted to study if IGF I had effects on sex-differentiated CYP enzymes and to compare he effects of IGF-I to, the effects of GH. IGF-I, GH or saline was adm inistered continuously via osmotic minipumps to normal and hypophysect omised rats for seven days. After treatment, the expression of several sex-differentiated liver enzymes (CYP2C11, CYP2C12), the female domin ant steroid 5 alpha-reductase, and the male-dominant CYP3A2 enzyme was studied at mRNA, protein and/or functional levels. Our results demons trate that IGF-T has marked effects on the sex specific expression of CYP2C11 and CYP2C12. The effects of IGF-I were similar to those of GH. In contrast, in hypophysectomised rats IGF-I gave effects opposite to those observed after GH treatment to normal rats on the CYP3A-associa ted cortisol 6 beta-hydroxylation. No effects of IGF-I on the steroid 5 alpha-reductase activity were observed. BIOCHEM PHARMACOL 56;4:459-4 66, 1998. (C) 1998 Elsevier Science Inc.