Abstract: 56

ESTRADIOL REGULATES GONADOTROPIN-RELEASING HORMONE (GnRH) AND GnRH RECEPTOR MESSENGER RIBONUCLEIC ACID (mRNA) LEVELS IN HUMAN GRANULOSA-LUTEAL CELLS.

Parimal S. Nathwani¹ , Sung Keun Kang¹ , Kwai Wa Cheng¹ , Peter C. K. Leung^{1 *}
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.