CHARACTERIZATION OF ESTROGENICITY OF PHYTOESTROGENS IN AN ENDOMETRIAL-DERIVED EXPERIMENTAL-MODEL

Severe developmental and reproductive disorders in wild animals have b een linked to high exposure to persistent environmental chemicals with hormonal activity These adverse effects of environmental estrogens ha ve raised considerable concern and have received increasing attention. Although numerous chemicals with the capacity to interfere with the e strogen receptor (ER) have been identified, information on their molec ular mechanism of action and their relative potency is rather limited. For the endometrium, the lack of information is due to the lack of a suitable experimental model. We investigated the functions of phytoest rogens in an endometrial-derived model, RUCA-I rat endometrial adenoca rcinoma cells. The cells were cultured on a reconstituted basement mem brane to preserve their functional differentiation and estrogen respon siveness. We assessed the relative binding affinity to the estrogen re ceptor of the selected phytoestrogens coumestrol, genistein, daidzein, and the putative phytoestrogen mangostin compared to estradiol by a c ompetitive Scatchard analysis. The following affinity ranking was meas ured: 17 beta-estradiol >>> coumestrol > genistein > daidzein >>> mang ostin. In addition, we investigated the capacity of these compounds to promote the increased production of complement C3, a well-known estra diol-regulated protein of the rat endometrium. All substances tested i ncreased the production of complement C3, although different concentra tions were necessary to achieve equivalent levels of induction compare d to estradiol. Mechanistically we,were able to demonstrate that the i ncrease of complement C3 production was mediated by primarily increasi ng its steady-state mRNA level. These findings indicate that RUCA-I ce lls represent a sensitive model system to elucidate relative potencies and functions of environmental estrogens in an endometrium-derived mo del.