Some controversy persists regarding the intra-ovarian localization of estrogen receptors (ER) in primates. while the presence of ER in the germinal epithelium of the ovary is well documented, we now demonstrate ER in other compartments, such as macaque corpus luteum tissue and human granulosa cells (GC) from women participating in an in-vitro fertilization program. Since ER is known to be modulated by certain xenobiotics such as 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD), we wished to ascertain whether the dioxin receptor (the aromatic hydrocarbon receptor, AHR) is also present in these tissues. The AHR is a ligand-inducible transcription factor found in a variety of vertebrate species. It is a soluble receptor known to bind a variety of halogenated aromatic hydrocarbons (HAH). TCDD, the most potent of the HAH, has been shown to exert its anti-fertility effects in several species, and is implicated in developmental defects in female rats and primates, presumably by modulating estrogen action. In the present study we show, by gel-shift assays, the presence of ER capable of binding DNA within the Rhesus macaque ovary and extend these findings to the human ovary; specifically GC. Estrogen receptor is present in macaque corpus luteum tissues by western blot analysis, using H222 and H226 monoclonal antibodies; and ER mRNA is expressed in human GC using reverse-transcription polymerase chain reaction (RT-PCR). We further localize the AHR to the macaque and human ovary by gel-shift assays, and by western blot analysis, using the PA3-513 polyclonal antibodies. Based upon this and other evidence of the effects of dioxins on reproductive function, the present study strongly supports a local role for the interplay between the estrogen- and AHR-signaling systems in the primate ovary. Further research in this area should enhance our understanding of the role of environmental pollutants in reproductive function in primates. Key words

National Institute of Health (NIH)
National Center for Research Resources (NCRR)
Primate Research Center Grants (P51)
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University of Wisconsin Madison
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