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Parimal S. Nathwani1 , Sung Keun Kang1 , Kwai Wa Cheng1 , Peter C. K. Leung1 *
Department of Obstetrics and Gynaecology, University of British Columbia, Vancouver, BC, Canada 1
The identification of ovarian gonadotropin releasing hormone (GnRH) and its receptor (GnRH-R), and its involvement in inducing cell death during the follicular and luteal phase, suggests an important autocrine/paracrine role for GnRH in the ovary. However, the factors that regulate expression of ovarian GnRH and GnRH-R remain poorly characterized to date. As gonadal steroids are key regulators of ovarian function, it is tempting to investigate the role of estradiol in regulating ovarian GnRH and GnRH-R expression. Using reverse transcription polymerase chain reaction (RT-PCR), we have isolated the full-length GnRH-R coding region from human granulosa- luteal cells (hGLCs). On day 5 in culture, hGLCs (n=4) were treated with various concentrations of E2 (1-100nM). A dose-dependent decrease (p<0.05) in GnRH and GnRH-R was observed after 24h treatment. Time course studies indicated that a short-term treatment (6h) with E2 (1nM) had no significant effect on GnRH mRNA levels. However, a long- term treatment (48h) resulted in a 40% decrease in GnRH expression (p<0.05). Interestingly, GnRH-R expression exhibited a biphasic pattern with time. A 6h treatment with E2 (1nM) resulted in a 20% increase in GnRH-R message (p<0.05), whereas a long term treatment (48h) resulted in a 60% decrease in GnRH-R expression (p<0.05) in hGLCs. Tamoxifen treatment reversed the effect of E2 on GnRH and GnRH-R expression, indicating that the E2 effect was mediated through its receptor. In summary, our studies demonstrate that E2 has a negative effect on GnRH and GnRH-R expression in hGLCs. Functionally, the down regulation of GnRH and its receptor by E2, may contribute to the appropriate development of the corpus luteum.
This abstract is being presented on Sunday, August 1 at 8:00 AM to 10:15 AM at CUB 2nd Floor Ballroom.