Effect of tamoxifen treatment on liver, lung and intestinal mixed-function oxidases in male and female rats

Tamoxifen is a nonsteroidal antiestrogen which is used as an adjuvant form of chemotherapy for breast carcinomas containing estrogen receptors. Tamoxifen citrate (2 mg/rat/day) administration to male rats significantly decreased hepatic microsomal aryl hydrocarbon hydroxylase and 7-ethoxycoumarin O-de-ethylase activities and cytochrome P-450 content. These effects may be exerted through an antiandrogenic activity of tamoxifen, because plasma testosterone concentrations were also decreased. In male rats, tamoxifen treatment also depressed lung and intestinal microsomal aryl hydrocarbon hydroxylase and 7-ethoxycoumarin O-de-ethylase activities. Tamoxifen citrate treatment of female rats had no effect on hepatic, pulmonary, or intestinal microsomal aryl hydrocarbon hydroxylase or 7-ethoxycoumarin O-de-ethylase activities or hepatic cytochrome P-450 content. The results support the contention that estrogens at physiologic levels do not exert a significant regulatory effect on xenobiotic metabolism. Furthermore, androgens are known to influence drug metabolism, and the results indicate that tamoxifen has some antiandrogenic activity.