1-(o-chlorophenyl)-1-(p-chlorophenyl)2,2,2-trichloroethane: a probe for studying estrogen and progestin receptor mediation of female sexual behavior and neuroendocrine responses.

A number of chlorinated insecticides have been shown to interact with estrogen receptors and to mimic estrogen action in peripheral reproductive tissues (e.g. vagina and uterus). The present study was designed to assess whether the dichlorodiphenyltrichloroethane (DDT) isomer o,p'-DDT has estrogenic or antiestrogenic activity in neural estrogen target tissues. Single sc injections of up to 500 mg/kg o,p'-DDT had no effect on female sexual behavior (lordosis). However, more prolonged treatments induced high levels of lordosis behavior, inhibited compensatory ovarian hypertrophy, and reduced body weight gain in ovariectomized adult female rats. Since o,p'-DDT was able to mimic the action of estrogen on these three neuroendocrine responses, further experiments were performed to determine whether the compound could be used as a tool to investigate the role of hypothalamic steroid receptors in estrogen stimulation of reproductive behavior. It was found that single injections of 500 mg/kg o,p'-DDT (which did not induce sexual receptivity) interacted with cytosol estrogen receptors in both the hypothalamus and pituitary. However, depletion of cytosol receptors by o,p'-DDT was very slow and incomplete; maximal depletion was only 51% and did not occur until 8 h postinjection. It was also observed that neither behaviorally effective nor ineffective injections of o,p'-DDT were able to induce progestin receptor synthesis in the hypothalamus or pituitary. Thus, it appears that the inability of the compound to promote lordosis behavior after a single injection probably results from inadequate receptor interaction in hypothalamic cell nuclei, but that failure to induce neural progestin receptor synthesis is not the critical factor. These data also suggest that the study of o,p'-DDT action in the brain may provide useful information regarding mechanisms of steroid mediation of neuroendocrine responses.