PARENT SESSION
PLATFORM SESSION 15. NEUROENDOCRINOLOGY

Tuesday, August 3, 2004
4:30 PM–6:30 PM
Buchanan A104
Chair: Matt Hardy Co-Chair: Leslie Jackson

(552) DIFFERENTIAL ROLE OF PROGESTERONE IN THE GONADOTROPIN-RELEASING HORMONE (GNRH) SYSTEM, AND FUNCTION OF GNRH I AND II ON THE TRANSCRIPTIONAL ACTIVITIES OF SEX STEROID HORMONE RECEPTORS.

An, Beum-Soo¹, Choi, Jung-Hye¹, Choi, Kyung-Chul¹, Leung, Peter C. K.¹, ¹ Department of Obstetrics and Gynecology, University of British Columbia, Vancouver, BC, Canada

ABSTRACT- It is hypothesized that sex steroids may regulate gonadotropin-releasing hormone I (GnRH I; a classical form of GnRH), GnRH II (a second form of GnRH) and GnRH receptor (GnRHR) at the transcriptional level in target tissues. In addition, it has been reported that sex steroid receptors could be activated by GnRH I in the absence of ligands. Thus, we investigated the action of progesterone (P4) in the regulation of GnRH system at the mRNA and transcriptional levels. TE671, a human neuronal cell line, was used as a cell model as previous studies have reported the expression of both GnRH I and GnRH II in these cells. Treatment of TE671 cells with P4 resulted in a decrease of GnRHR promoter activity and an increase of GnRH I transcripts, however, no significant change was observed in the expression level of GnRH II mRNA by P4. To determine the signaling pathway involved in the action of P4, progesterone receptor A (PR A) or PR B plasmid was transiently transfected into the cells. It appears that PR B is mediated in the stimulating effect of P4 on GnRH I gene, whereas, PR A is involved in the P4-induced repression on the GnRHR promoter. PR B exerted a dominant negative effect on PR A-induced repression in the activity of GnRHR promoter in the presence of P4. These results indicate that P4 is a potent regulator of GnRH system at the transcriptional levels in TE-671 cells. The differential effects of P4 on GnRH system may be mediated from distinct pathway through PR A or PR B. In addition, we examined the ligand-dependent activation of estrogen receptor (ER) and PR by GnRH I and II in the different cell lines including pituitary and neuronal cells. We transfected the cells with a reporter gene which has hormone response element (HRE) in the upstream of the promoter. After treatment with GnRH I and II, we evaluated transcriptional activities of ER and PR by luciferase assay. Both GnRH I and II induced the transcriptional activities of ER and PR through the HRE in a ligand-independent manner, and this effect is cell- and tissue-specific. Taken together, P4 has distinct effects on GnRH system via diverse mechanisms, in contrast, GnRH I and II regulate the transcriptional activities of sex steroid receptors in a cell- and tissue-specific manner. [This work was supported by the Canadian Institutes of Health Research.]

KEY WORDS: E2 and P4, Transcriptional regulation, GnRH, ER and PR