Diminished prolactin from chlordecone treatment in ovariectomized (NZB×NZW)F1 mice

In murine models of systemic lupus erythematosus (SLE), administration of either prolactin or estradiol (E2) increases autoimmunity, and there is evidence that elevated prolactin in response to E2 administration may contribute substantially to E2 effects. Hormonal influence on SLE can extend to environmental agents, as demonstrated by the ability of estrogenic organochlorine pesticides such as chlordecone to accelerate the development of lupus in female (NZB × NZW)F 1 mice. In order to evaluate a potential role for prolactin in chlordecone effects on SLE, it was necessary to first determine whether treatment with chlordecone, like E2, results in elevated prolactin levels. Ovariectomized (NZB × NZW)F 1 mice were treated for 5–6 weeks with chlordecone or E2 in doses shown previously to significantly shorten the time to onset of SLE. At the end of the treatment period, serum prolactin levels were increased 10- to 20-fold in E2-treated mice compared to untreated controls, but decreased in an apparent dose-dependent manner in mice treated with chlordecone. Prolactin receptor in purified splenic B and CD4 T cells from treated animals, assessed through measurement of mRNA using quantitative real-time PCR, was increased by E2 treatment but unchanged in response to chlordecone. These observations suggest that the role of prolactin in eliciting autoimmunity in E2-treated animals is absent in the case of chlordecone, and by implication, that chlordecone possesses other actions that can replace the contribution of prolactin to development of SLE.