Androgen Effects Mediated by Estrogen Receptor in 7,12- Dimethylbenz(a)anthracene-induced Rat Mammary Tumors1

To improve our understanding of the effects of androgens on the induction and growth of mammary tumors, the interaction of androgen on the estrogen receptor (ER) has been evaluated in the 7,12-dimethylbenz(a)anthracene-induced rat mammary tumor. In vitro competitive experiments have shown that androgens interact on ER with a low affinity but have a good stereospecificity for C,9 steroids bearing a 170and/or 3/3-hydroxyl group. The administration of one dose ( -20 mg) of 5a-dihydrotestosterone to 1-day ovariectomized rats induced ER nuclear translocation in 92% of the mammary tumors. In 60% of these tumors, this translocation was followed by a signifi cant stimulation of the rate of [3H]leucine incorporation into cytosoluble proteins by 5a-dihydrotestosterone or estradici. When injected together, 5a-dihydrotestosterone did not antagonize the effect of estradiol. We conclude that one very high dose of 5a-dihydrotestosterone that stimulates leucine incorporation into pro teins is also able to occupy the cytosol ER in mammary tumors and to translocate it in vivo into the nucleus. We suggest that a direct interaction of androgens with the ER located in mammary tumors is responsible, as in rat uteri, for the stimulating effect of very high doses of androgens. We cannot ascertain that the same mechanism is involved in the androgen-induced regression of the mammary tu mors.