Anti-estrogenic action of chlordecone in rat pituitary gonadotrophs in vitro.
Estradiol-17 beta (E2) enhances the response of rat pituitary gonadotrophs to gonadotrophin-releasing hormone (GnRH) in vitro. This effect of E2 on rat gonadotrophs in vitro was applied as a model to study the estrogenic or anti-estrogenic activity of chlordecone in gonadotrophs. Rat pituitary cell cultures were treated with E2 (10(-10) M), chlordecone (10(-7) to 10(-5) M), or both before a 6-hr challenge of D-Lys6-GnRH (GnRH-A). Secretion of luteinizing hormone (LH) and follicle-stimulating hormone (FSH) during the 6-hr of GnRH-A treatment was measured. Pretreatment of cells with E2 for 2 days increased the GnRH-A-stimulated LH and FSH secretion approximately twofold. This effect of E2 was antagonized by the coexistence of chlordecone in a dose-dependent manner. The effect of E2 (10(-10) M) could be totally abolished by 10(-6) M chlordecone. Further, chlordecone alone had little or no effect on basal secretion of LH and FSH, but it significantly suppressed the response of gonadotrophs to GnRH-A. [Mirex, a compound with a similar chemical structure to chlordecone, did not suppress GnRH-A-stimulated secretion of LH or FSH under any condition tested.] The present study demonstrated that chlordecone had two specific effects on rat pituitary gonadotrophs: (1) to antagonize the effects of estrogen, and (2) to reduce the response of gonadotrophs to GnRH-A. Thus, chlordecone is not estrogenic in rat pituitary cells in vitro.
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Huang
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Nelson
D000818:Animals; D007631:Chlordecone / Q000494:pharmacology*; D004958:Estradiol / Q000494:pharmacology; D005260:Female; D005640:Follicle Stimulating Hormone / Q000378:metabolism; D007987:Gonadotropin-Releasing Hormone / Q000031:analogs & derivatives / Q000494:pharmacology; D066298:In Vitro Techniques; D007306:Insecticides / Q000494:pharmacology*; D007986:Luteinizing Hormone / Q000378:metabolism; D008917:Mirex / Q000494:pharmacology; D010902:Pituitary Gland / Q000166:cytology / Q000187:drug effects*; D051381:Rats; D011919:Rats, Inbred Strains
D007306:Insecticides; D007987:Gonadotropin-Releasing Hormone; D004958:Estradiol; C010661:surfagon; D007986:Luteinizing Hormone; D005640:Follicle Stimulating Hormone; D007631:Chlordecone; D008917:Mirex