Estrogenic effects of organochlorine pesticides on uterine leiomyoma cellsin vitro

Although benign, uterine leiomyomas occur with high frequency and significa nt morbidity in reproductive-age women, and they present a significant heal th problem. Leiomyomas develop in the uterine myometrium and are sensitive to ovarian hormones, making them potential target sites for endocrine disru pters. Here we utilize cell lines derived from rat uterine leiomyomas to de termine if a panel of 7 organochlorine pesticides have potential agonist ac tivity in myometrial cells using cellular and molecular in vitro assays. Th e organochlorine pesticides investigated have been previously characterized as having agonist activity in other hormonally responsive tissues, but the ir effects have not been studied in uterine myometrial cells. In Eker rat l eiomyoma-derived cells, HPTE, kepone, and the alpha isomer of endosulfan st imulated proliferation, an effect dampened by the antiestrogen ICI 182,780. In addition, these compounds stimulated transcription of the vitellogenin estrogen-response element via the ER in a transcriptional reporter gene ass ay and induced the expression of an endogenous estrogen-responsive gene, th e progesterone receptor (PR). This contrasted with the agonist profile of m ethoxychlor, dieldrin, toxaphene, and endosulfan-beta. These compounds, una ble to stimulate proliferation of uterine leiomyoma cells, did exhibit agon istic activity in these cells at the transcriptional level in the estrogen- sensitive reporter gene assay, and they were also able to upregulate PR mes sage. These data demonstrate that organochlorine pesticides act as estrogen receptor agonists in Eker rat uterine myometrial cells, and they indicate a need for further investigation of the potential tissue-specific agonist a ctivity of these pesticides and their role in the pathogenesis of uterine l eiomyoma.