| Characterization of Estrogenicity of Phytoestrogens in an Endometrial-derived Experimental Model Anne-Christine Hopert, Antje Beyer, Kirsten Frank, Elisabeth Strunck, Winfried Wünsche, and Günter Vollmer Institut für Molekulare Medizin, Medizinische Universität zu Lübeck, Lübeck, Germany Abstract
Severe developmental and reproductive disorders in wild animals have been linked to high exposure to persistent environmental chemicals with hormonal activity. These adverse effects of environmental estrogens have raised considerable concern and have received increasing attention. Although numerous chemicals with the capacity to interfere with the estrogen receptor (ER) have been identified, information on their molecular 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 phytoestrogens in an endometrial-derived model, RUCA-I rat endometrial adenocarcinoma cells. The cells were cultured on a reconstituted basement membrane to preserve their functional differentiation and estrogen responsiveness. We assessed the relative binding affinity to the estrogen receptor of the selected phytoestrogens coumestrol, genistein, daidzein, and the putative phytoestrogen mangostin compared to estradiol by a competitive Scatchard analysis. The following affinity ranking was measured: 17ß-estradiol >>> coumestrol > genistein > daidzein >>> mangostin. In addition, we investigated the capacity of these compounds to promote the increased production of complement C3, a well-known estradiol-regulated protein of the rat endometrium. All substances tested increased the production of complement C3, although different concentrations were necessary to achieve equivalent levels of induction compared to estradiol. Mechanistically we were able to demonstrate that the increase of complement C3 production was mediated by primarily increasing its steady-state mRNA level. These findings indicate that RUCA-I cells represent a sensitive model system to elucidate relative potencies and functions of environmental estrogens in an endometrium-derived model. Key words: binding affinity, complement C3, endometrium, estrogen receptor, extracellular matrix, phytoestrogens. Environ Health Perspect 106:581-586 (1998) . [Online 12 August 1998] http://ehpnet1.niehs.nih.gov/docs/1998/106p581-586hopert/ abstract.html Address correspondence to A.-C. Hopert, Institut für Molekulare Medizin, Medizinische Universität zu Lübeck, Ratzeburger Allee 160, D-23538 Lübeck, Germany. We thank Elrina Joubert for her careful and critical reading of the manuscript. This work was supported by PUG U 96003, Forschungszentrum Karlsruhe. Received 2 January 1998 ; accepted 19 May 1998. Address correspondence to A.-C. Hopert, Institut für Molekulare Medizin, Medizinische Universität zu Lübeck, Ratzeburger Allee 160, D-23538 Lübeck, Germany. We thank Elrina Joubert for her careful and critical reading of the manuscript. This work was supported by PUG U 96003, Forschungszentrum Karlsruhe. Received 2 January 1998 ; accepted 19 May 1998.
The full version of this article is available for free in HTML format. |
