Differing effects of endocrine-disrupting chemicals on basal and FSH-stimulated progesterone production in rat granulosa-luteal cells

Previous studies have shown that the phytoestrogen, genistein, inhibits bas al and forskolin-stimulated progesterone synthesis in rat granulosa-luteal cells. Genistein, however, not only binds and activates the estrogen recept or (ER), but is also a potent inhibitor of tyrosine kinase. In these studie s we have compared the effects of estradiol, two other phytoestrogens, apig enin 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 produc tion in the same experimental system. Only a supraphysiological dose of est radiol (10(-5) M) significantly inhibited basal and forskolin-stimulated pr ogesterone production in granulosa-luteal cells, but had no effect on FSH-s timulated production. In contrast, apigenin, DDT, and octyl-phenol stimulat ed basal progesterone production at doses around 10(-8) to 10(-7) M, but th is effect was reversed at higher doses. Coumarin was without effect. Like b asal production, the two phytoestrogens had opposing effects on FSH-stimula ted progesterone production. Genistein at 10(-5) M was inhibitory, while ap igenin 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 ne arly doubled the response. While all these chemicals are known to interact with the estrogen receptor to a greater or lesser extent, these studies sug gest that like genistein, these different endocrine-disrupting chemicals ma y have other actions apart from those on the estrogen receptor.