Effects of testosterone and estrogen on hepatic levels of cytochromes P450 2C7 and P450 2C11 in the rat.
The effects of exogenous hormone treatment on the expression of cytochromes P450 2C7 and P450 2C11 were studied in neonatally gonadectomized and sham-operated male and female rats. Hepatic levels of cytochrome P450 2C7 were found to be two- to threefold higher in intact adult female versus male rats. Neonatal gonadectomy resulted in a reversal of the relative cytochrome P450 2C7 levels in male and female animals at maturity. Expression of this isozyme was restored in ovariectomized females by estradiol treatment. Furthermore, neonatal and/or pubertal administration of estradiol to intact male rats induced cytochrome P450 2C7 to adult female levels. On the other hand, administration of testosterone at all times examined had no effect in intact female rats, but decreased cytochrome P450 2C7 to normal levels in neonatally castrated males treated during adulthood. Neonatal testosterone treatment also increased hepatic cytochrome P450 2C7 content in both ovariectomized females and intact males. These results indicate that estrogen is required for full expression of cytochrome P450 2C7 while the effect of testosterone is ambiguous. In comparison, neonatal gonadectomy of male rats abolished the adult expression of cytochrome P450 2C11. Normal levels were restored only by treatment with testosterone during adulthood. Neonatal testosterone treatment did not induce cytochrome P450 2C11 levels in gonadectomized rats of either sex. In contrast, neonatal estrogen treatment suppressed cytochrome P450 2C11 expression in intact adult male rats to the same extent as neonatal castration. These results indicate that androgen exposure during the adult, and not the neonatal, phase is essential for full expression of cytochrome P450 2C11.
Bandiera
S
S
Faculty of Pharmaceutical Sciences, University of British Columbia, Vancouver, Canada.
Dworschak
C
C
D000375:Aging; D000704:Analysis of Variance; D000818:Animals; D000831:Animals, Newborn; D001189:Aryl Hydrocarbon Hydroxylases; D001835:Body Weight / Q000187:drug effects; D003577:Cytochrome P-450 Enzyme System / Q000302:isolation & purification / Q000378:metabolism*; D004958:Estradiol / Q000494:pharmacology*; D005260:Female; D007700:Kinetics; D008099:Liver / Q000187:drug effects / Q000254:growth & development; D008297:Male; D008862:Microsomes, Liver / Q000187:drug effects / Q000201:enzymology*; D009919:Orchiectomy; D009929:Organ Size / Q000187:drug effects; D010052:Ovariectomy; D051381:Rats; D012016:Reference Values; D012727:Sex Characteristics; D039181:Steroid 16-alpha-Hydroxylase; D013250:Steroid Hydroxylases / Q000302:isolation & purification / Q000378:metabolism*; D013739:Testosterone / Q000097:blood / Q000494:pharmacology*
D013739:Testosterone; D004958:Estradiol; D003577:Cytochrome P-450 Enzyme System; D013250:Steroid Hydroxylases; D001189:Aryl Hydrocarbon Hydroxylases; D039181:Steroid 16-alpha-Hydroxylase