ESTROGEN AND ANDROGEN RECEPTOR-MEDIATED STIMULATION AND INHIBITION OF PROLIFERATION BY ANDROST-5-ENE-3-BETA,17-BETA-DIOL IN HUMAN MAMMARY-CANCER CELLS

Androst-5-ene-3beta,17beta-diol (ADIOL) and 5alpha-androstane-3beta,17beta-diol (5alphaA), which are metabolites of dehydroepiandrosterone and dihydrotestosterone, are known to have estrogenic properties. This study reevaluates the estrogenic effects of ADIOL and 5alphaA in MCF-7 cells and demonstrates additionally androgen-like inhibitory properties of these compounds in human hormone-dependent mammary cancer cells. ADIOL and 5alphaA (10-100 nM) stimulate the proliferation of estrogen-sensitive MCF-7 cells. Binding assays with the estrogen receptor and inhibition of stimulation with the antiestrogen tamoxifen support the involvement of the estrogen receptor. On the other hand, the mammary cancer cell line MFM-223 is strongly inhibited by ADIOL and 5alphaA in the same concentration range. This cell line is androgen receptor positive and is inhibited by androgens, but unresponsive to estrogens and progestins. The inhibitory effects of ADIOL and 5alphaA in MFM-223 cells are mediated by the androgen receptor as demonstrated by receptor studies and competition experiments with hormone antagonists. ADIOL and 5alphaA thus possess estrogen- and androgen-like properties and can stimulate or inhibit proliferation of human mammary cancer cells. The reactions of mammary cancer cells to these steroids depend on the receptor content and the growth properties of the individual cell line.