Chlorinated pesticides such as DDT, chlordecone, lindane, methoxychlor, toxaphene and dieldrin are recognized for their neuroexcitatory effects. Many are also recognized for their reproductive toxicity but, until recently, few attempts had been made to relate these two manifestations. After a relatively short-term exposure condition in female rats, chlordecone has been demonstrated to alter several indices of female reproductive competence including inhibition of estrogen mediated changes in CNS progesterone receptors, pituitary LH release and sexual behavior. Chlordecone disrupted estrous cycle changes in serotonin receptors and reduced fertility under various exposure conditions. Results of these studies have suggested a dual mode of neuro-reproductive toxicity exerted by chlorinated pesticides. One mode involves the pesticide's antiestrogenic action at the CNS estrogen receptor and the other involves the disruption of neurotransmitter function. Disruptions of reproductive behaviors after diestrous exposure rely primarily upon antiestrogenic actions while exposure near the period of ovulation may involve serotonergic mechanisms. The studies are designed to evaluate this dual mechanism hypothesis by investigating o,p-DDT (which has affinity for the estradiol receptor but no reported actions on serotonin) and p,p'-DDT (which disrupts serotonergic function but has no special affinity for the estradiol receptor). Lindane and toxaphene, representing two additional classes of chlorinated compounds, will be investigated to evaluate the generality of the dual mechanism hypothesis. These studies are of considerable health significance since it has been thought that the """"""""estrogenicity"""""""" of the chlorinated pesticides provided the greates threat to reproductive competence. These studies will also provide a framework for the classification of chlorinated pesticides according to their mode of disruption of reproductive function. It is particularly important that both proposed mechanisms are postulated to decrease sexual behavior. If this prediction is verified, sexual receptivity in female rodents could become an effective screening tool for evaluation of other potential neuro-reproductive toxicants. Since the measurement of rodent sexual receptivity requires neither complex behavioral nor biochemical instrumentation, it could easily be introduced into ongoing toxicological programs. These studies will also provide a model for further understanding of estrogen's facilitation of sexual behavior.
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