Chlorinated, hydrocarbon pesticides, such as DDT and Chlordecone (Kepone Registered Trademark), are recognized for both their neurotoxicity and their reproductive toxicity. Until recently, few attempts had been made to relate these two mainfestations of toxicity and these had relied upon long-term exposure designs. The hypothalamicpituitary axis (via luteinizing hormone (LH) and follicle stimulating hormone (FSH) regulates gonadal function, but gonadal secretions (e.g. estrogen and progesterone in the female and testosterone in the male) feed back on both the hypothalamus and the pituitary to modify neural activity and the release of pituitary hormones. With long-term exposure, neuroendocrine changes could result from disruption of these feedback loops as well as direct neural/pituitary actions of the pesticide. Using a short-term exposure design, we have obtained evidence for direct neuroen docrine effects of chlordecone. Female rats were examined 8-60 hours after exposure to chlordecone. Effects of chlordecone were seen on the CNS estrogen receptor, on hypothalamic serotonin systems, on neuroendocrine parameters and on sexual behavior. Some of the data are compatible with a weak estrogen-like action of chlordecone, but overall, the data suggest that chlordecone mimicked the negative feedback effects of estradiol on the hypothalamic-pituitary axis but that the pesticide inhibited the positive feedback actions of estradiol on LH release and on sexual receptivity in the adult female. Studies are proposed to examine these findings. Three mechanisms for chlordecone's antagonism of the facilitory role of estradiol are postulated: (1) Chlordecone inhibits the induction of brain progesterone receptors. (2) Chlordecone disrupts neurotransmitter changes in response to estradiol. (3) Chlordecone directly affects anterior pituitary sensitivity to luteinizing hormone releasing factor (LHRH). These studies will contribute to the understanding of chlorinated pesticides' neural and reproductive effects. They will also provide an impetus for the inclusion of neuroendocrine parameters in the study of neurotoxicity.
NIH ExPorter
NIH ExPorter