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ORIGINAL ARTICLE

Differing Effects of Endocrine-Disrupting Chemicals on Basal and FSH-Stimulated Progesterone Production in Rat Granulosa-Luteal Cells

Department of Physiology, St. George's Hospital Medical School, Cranmer Terrace, London SW170RE, United Kingdom

Previous studies have shown that the phytoestrogen, genistein, inhibits basal and forskolin-stimulated progesterone synthesis in rat granulosa-luteal cells. Genistein, however, not only binds and activates the estrogen receptor (ER), but is also a potent inhibitor of tyrosine kinase. In these studies we have compared the effects of estradiol, two other phytoestrogens, apigenin and coumarin, the pesticide, [2-(chlorphenyl)-2-(4-chlorphenyl)-1,1,1-trichlorethan] (2,4'DDT), and the industrial chemical, 4-octyl-phenol, on basal and follicle stimulating hormone (FSH)-stimulated progesterone production in the same experimental system. Only a supraphysiological dose of estradiol (10^-5 M) significantly inhibited basal and forskolin-stimulated progesterone production in granulosa-luteal cells, but had no effect on FSH-stimulated production. In contrast, apigenin, DDT, and octyl-phenol stimulated basal progesterone production at doses around 10^-8 to 10^-7 M, but this effect was reversed at higher doses. Coumarin was without effect. Like basal production, the two phytoestrogens had opposing effects on FSH-stimulated progesterone production. Genistein at 10^-5 M was inhibitory, while apigenin significantly potentiated the response at 19^-7 M. In contrast, DDT had no effect on the FSH-induced response, though 10^-7 M octyl-phenol nearly doubled the response. While all these chemicals are known to interact with the estrogen receptor to a greater or lesser extent, these studies suggest that like genistein, these different endocrine-disrupting chemicals may have other actions apart from those on the estrogen receptor.

Key Words: endocrine-disrupting chemicals • phytoestrogens • progesterone • granulosa-luteal cells • FSH

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