MOLECULAR MECHANISMS OF TCDD INDUCED ANOVULATION

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DESCRIPTION: This proposal is designed to test the hypothesis that TCDD inhibits ovulation by interruption of estrogen receptor (ER) and/or progesterone receptor (PR) mediated transcriptional activation of target genes in ovarian follicles. One specific aim is to determine cellular targets for TCDD action in the ovary by localizing aryl hydrocarbon receptors (Ah-Rs) and Ah-R nuclear translocators (ARNTs), utilizing in situ hybridizations in immature rat ovaries at various stages of follicular development and ovulation. The second specific aim is to determine whether and at what level TCDD alters the ER and/or PR mediated signaling pathways in the ovary. The ER and PR expression in the ovary will be analyzed by mRNA analysis by in situ hybridization or RT-PCR and through protein analysis using Western blots from immature gonadotropin treated rat ovaries. The ability of TCDD to inhibit estrogen or progesterone stimulated target gene transcription will be studied by examining the binding ability of Ers and Prs to DNA (gel shift analysis) and the ability to transcribe the promoter of target genes.