Estrogen-induced tumorigenesis in hamsters: roles for hormonal and carcinogenic activities

Based on the experimental studies presented herein, we have concluded there are hormonal and carcinogenic aspects to estrogens, both natural and synthetic, which are involved in renal tumorigenesis in the hamster. Hormonal aspects related to this tumor system are based on the presence of specific estrogen receptor in the untransformed kidney which is elevated by prolonged estrogen treatment. Moreover, antiestrogens, which inhibit estrogen receptor complex binding activity, completely block renal tumor induction by estrogens. Finally, estrogens were found to induce progesterone receptor in the hamster kidney and this induction can be inhibited by androgens and antiestrogens. Carcinogenic aspects related to renal tumorigenesis are suggested by the marked suppression of estrogen-induced kidney tumors by alpha-naphthoflavone. In addition, ethinyl estradiol, as potent an estrogen in the hamster as either DES of 17 beta-estradiol, induced only a very low renal tumor incidence. The finding that aryl hydrocarbon hydroxylase activity in the hamster kidney, but not the liver, is depressed markedly by estrogens and enhanced by androgenic hormone suggests involvement of the microsomal monooxygenase system in affecting estrogen metabolism and ultimately perhaps its carcinogenicity.