Effect of tamoxifen on hepatic cytochrome P450 expression in adult female rats
Abstract
Tamoxifen, a widely used therapeutic agent in the treatment of breast cancer, is known to suppress growth hormone (GH) secretion in rats and consequently may alter hepatic levels of several cytochrome P450 (CYP) isozymes that are regulated by the pattern of GH secretion. The present study was undertaken to examine the effect of tamoxifen on the expression of hepatic CYP enzymes in the rat. Tamoxifen was administered to nine adult male and female Long Evans rats at a dose of 5 mg per rat s.c. once daily for two consecutive days while control rats received the vehicle (peanut oil) only. Rats were killed five weeks after treatment and liver microsomes prepared. Administration of tamoxifen resulted in a significant decrease in mean weight gain in male and female rats compared to controls, but liver weight as a percent of body weight was not affected. Serum estradiol levels and total CYP content of hepatic microsomes were also unchanged. The profile of testosterone metabolites was not affected in tamoxifen-treated male rats but was significantly (p<0.05) altered in tamoxifen-treated female rats, indicating that tamoxifen's effects were sex-specific and hormone-mediated. Tamoxifen treatment significantly increased testosterone 6p-hydroxylase activity and significantly decreased testosterone 7a-hydroxylase activity but did not significantly affect j9-nitrophenol hydroxylase or pentoxyresorufin O-depentylase activities. Immunoquantitation studies revealed that tamoxifen treatment…
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