DEHYDROEPIANDROSTERONE-SULFATE ESTROGENIC ACTION AT ITS PHYSIOLOGICALPLASMA-CONCENTRATION IN HUMAN BREAST-CANCER CELL-LINES

Estrogen receptor activation in hormone dependent cells (MCF-7 and T47 D) and hormone independent cells (MDA-MB-231) was measured by biolumin escence in stably transfected human breast cancer MCF-7, T47D and MDA- MB-231 cell lines with a reporter gene which allows expression of the firefly luciferase enzyme under the control of an estrogen regulatory element. Estrogen receptor activation by estrogens and steroid sulfate s such as estrone 3-sulfate (E1S), estradiol 3-sulfate (E2S), estriol 3-sulfate (E3S) and dehydroepiandrosterone sulfate (DHEAS) were studie d and compared in these cell lines. DHEAS, at a physiological plasma c oncentration only (1 mu M), had a high ''estrogen-like'' effect in MCF -7 and T47D cells. In contrast, estrogen sulfates did not have any eff ect on the luciferase activity at their physiological plasma concentra tion. These results suggest that MCF-7 and T47D cells could convert DH EAS to estrogens by aromatase and/or to estrogen-like compounds by oth er enzymatic systems. This is the first demonstrahon of the steroid su lfates action through their metabolites on the estrogen receptor. Ther efore, at the concentrations observed in physiological conditions, DHE AS could contribute to the pool of compounds having estrogenic activit ies in human breast cancer hormone dependent cell lines.