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THE PULSATILE RELEASE OF GONADOTROPIN-RELEASING HORMONE FROM FEMALE RAT HYPOTHALAMIC EXPLANTS IS NOT ALTERED BY 2,3,7,8-TETRACHLORODIBENZO-P-DIOXIN.
Trewin, Amanda1, Woller, Michael 2, Ho, Heather 1, Hutz, Reinhold1, 1 2
ABSTRACT- The environmental pollutant 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) is a potent endocrine disrupter. We have demonstrated previously that in-utero and lactational exposure to TCDD reduces serum estrogen concentrations in 21-day old female rats. We have further shown that this reduction in serum estrogen can be in part explained by a diminution in the number of large ovarian follicles. Although young are typically more sensitive than adults to TCDD, when administered to adult female rats TCDD also diminishes female reproductive function. Some evidence suggests that these effects are at least in part due to direct effects at the ovary. This study was conducted to investigate whether some of the adverse reproductive effects of TCDD are also mediated via the hypothalamic-pituitary axis. Hypothalami were collected at necropsy from normally cycling adult female rats on metestrus and proestrus. Hemihypothalamic tissues were cultured for six hours in an Endotronics Accusyst S Cell Perifusion System. Culture medium with or without 3.1 nM TCDD moved through the culture system at a rate of 1 ml per 10 minutes and was collected at 10-minute intervals. Samples were assayed for GnRH by RIA. GnRH release was pulsatile. TCDD had no effect on the pulsatility of GnRH release as there were no differences in the average peak interval between pulses, average peak amplitude, or baseline GnRH release. Based on these results, we were not able to verify any effects of TCDD on several parameters of hypothalamic release of GnRH but this does not preclude other deleterious effects of TCDD at the hypothalamus. Supported in part by NIH ES08342 and the Office of Research on Women's Health.
KEY WORDS: 2,3,7,8-tetrachlorodibenzo-p-dioxin, TCDD, GnRH, hypothalamus