There is growing concern that estrogenic chemicals, both natural and human-made, may be causing a variety of reproductive disorders in wildlife and human populations. Recent in vitro data suggest that the interaction between some weakly estrogenic organochlorines,
dieldrin,
endosulfan,
toxaphene, and
chlordane, causes a synergistic increase in their estrogenic potency, an effect due to joint action on
estrogen receptors (ER). As these studies were conducted using models of
estrogen action derived from cells that are not physiologically controlled by
estrogens, the relevance of these findings to human health are not clear. The present studies were conducted to examine the interaction between
endosulfan and
dieldrin in the activation of ER in or extracted from mammalian cells.
Endosulfan and
dieldrin showed no synergism in displacing 3H-E2 from rat uterine ER or in inducing the proliferation of MCF-7
breast cancer cells, an
estrogen-dependent response. Furthermore,
endosulfan (0.1 mg per animal per d) or
dieldrin (0.1 mg), alone or in combination, injected intraperitoneally daily for 3 d, did not stimulate any uterotrophic activity nor had any effect on pituitary
prolactin or other endocrine-related endpoints in immature female rats. These studies demonstrate that these weakly
estrogenic compounds do not interact in a synergistic fashion in binding to ER or in activating ER-dependent responses in mammalian tissues or cells. Thus, these results suggest that coexposure to these weakly estrogenic environmental contaminants likely will not cause human reproductive toxicity related to
estrogen action.