Effects of chlordecone administration on brain and pituitary peptide systems

It has been clearly demonstrated that chlordecone exerts estrogen-like effects on the reproductive system. However, the extent to which the estrogenic activity of this neurotoxicant may contribute to its central nervous system effects is not clear. The purpose of this study was to compare the estrogenic activity of chlordecone and estrogen on the rat hypothalamo-pituitary axis (HPA) by using the pituitary enkephalin system as a model. It was found that the enkephalin system of the anterior pituitary is regulated by circulating estrogen. Ovariectomy caused an increase in the pituitary content of enkephalin and this increase was prevented by estrogen treatment. Administration of estrogen reduced the pituitary content of this peptide in intact male rats. Similarly, chlordecone treatment reduced the pituitary content of enkephalin in a manner identical to that of estrogen. A single injection of chlordecone (75 mg/kg; i.p.) caused a delayed decrease in the enkephalin level of the anterior lobe (but not the posterior lobe) of the pituitary. This effect of chlordecone was selective to male rats since the pituitary enkephalin level of females was not altered by such treatment. Levels of other pituitary hormones such as beta-endorphin, vasopressin, etc., were not decreased. Further studies revealed that the similarities between chlordecone and estrogen could be extended to other pituitary hormones. For example, implantation of estrogen or of chlordecone in ovariectomized rats caused similar changes in serum prolactin and luteinizing hormone levels. Thus, this study demonstrates a clear estrogen-like action of chlordecone on the HPA. Moreover, due to the similarity of both estrogen and chlordecone to anti-dopaminergic agents in altering [Met5]-enkephalin levels in both the pituitary and caudate nucleus it is speculated that a dopaminergic mechanism is responsible for their actions on the enkephalin system.