Influence of tamoxifen on hormonally regulated cytochrome P450 enzyme expression in rats
Abstract
Tamoxifen, a partial estrogen antagonist in humans, is used widely in the treatment of breast cancer and suppresses growth hormone plasma levels in rats up to seven weeks after treatment. The purpose of the present study was to determine if tamoxifen treatment results in long-term alterations of hormonally regulated cytochrome P450 enzymes. Female rats were injected subcutaneously with tamoxifen at 0.5, 5, 20, 50, 100, or 200 mg/kg for two consecutive days. Male rats were injected subcutaneously with tamoxifen at 200 mg/kg for two consecutive days. Blood samples were taken at regular time intervals. Rats were killed 36 days after treatment and hepatic microsomes were prepared. Administration of tamoxifen decreased body weight gain in male and female rats. Testosterone 7α-hydroxylase activity and cytochrome P450 2A1 content were decreased in hepatic microsomes from tamoxifen treated female rats by 40% and 35%, respectively. In hepatic microsomes from tamoxifen treated male rats, testosterone 7α-hydroxylase activity was increased by 70% and testosterone 2a- and 16oc-hydroxylase activities and cytochrome P450 2C11 content was decreased by approximately 44% and 30%, respectively. Administration of tamoxifen decreased peak growth hormone plasma levels in male and female rats, but did not affect the average and nadir growth hormone plasma levels. In plasma of rats treated at 50 mg/kg, tamoxifen was detected at one day and at twelve days after treatment but not at 24 or 36 days…
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