Insulin-like growth factor 1 (IGF-I) effects on sex-specific cytochrome P450 enzymes in normal and hypophysectomised male rats.
The role of growth hormone (GH) in the regulation of the sex-differentiated 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 the effects of IGF-I to the effects of GH. IGF-I, GH or saline was administered continuously via osmotic minipumps to normal and hypophysectomised rats for seven days. After treatment, the expression of several sex-differentiated liver enzymes (CYP2C11, CYP2C12), the female-dominant steroid 5alpha-reductase, and the male-dominant CYP3A2 enzyme was studied at mRNA, protein and/or functional levels. Our results demonstrate that IGF-I 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-associated cortisol 6beta-hydroxylation. No effects of IGF-I on the steroid 5alpha-reductase activity were observed.
Department of Clinical Pharmacology, University Hospital, Uppsala, Sweden.
E
E
Rasmussen
B
B
Ask
N
N
Finnström
A
A
Skottner-Lundin
A
A
Rane
D000818:Animals; D001189:Aryl Hydrocarbon Hydroxylases; D042944:Cholestenone 5 alpha-Reductase; D051544:Cytochrome P-450 CYP3A; D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism*; D000072467:Cytochrome P450 Family 2; D013006:Growth Hormone / Q000097:blood; D006854:Hydrocortisone / Q000378:metabolism; D007016:Hypophysectomy; D007334:Insulin-Like Growth Factor I / Q000032:analysis / Q000494:pharmacology*; D008297:Male; D008565:Membrane Proteins; D010088:Oxidoreductases / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D012737:Sex Factors; D039181:Steroid 16-alpha-Hydroxylase; D013250:Steroid Hydroxylases / Q000378:metabolism*
D008565:Membrane Proteins; D007334:Insulin-Like Growth Factor I; D013006:Growth Hormone; D003577:Cytochrome P-450 Enzyme System; D010088:Oxidoreductases; D013250:Steroid Hydroxylases; D001189:Aryl Hydrocarbon Hydroxylases; C450279:CYP2C11 protein, rat; C465260:Cyp3a2 protein, rat; D051544:Cytochrome P-450 CYP3A; D000072467:Cytochrome P450 Family 2; D039181:Steroid 16-alpha-Hydroxylase; D042944:Cholestenone 5 alpha-Reductase; D006854:Hydrocortisone