Removal of REV-ERBα inhibition contributes to the prostaglandin G/H synthase 2 expression in rat endometrial stromal cells.

This study focused on Ptgs2, which is essential for decidualization, as a putative clock-controlled gene, and aimed to reveal the functions of clock genes in relation to Ptgs2 during decidualization. We compared the transcript levels of clock genes in the rat uterus on days 4.5 (D4.5) and 6.5 of pregnancy. The transcript levels of clock genes (Per2, Bmal1, Rorα and Rev-erbα) had decreased at implantation sites on day 6.5 (D6.5e) compared to those on D4.5, while Ptgs2 transcripts had increased on D6.5e. Similar observations of REV-ERBα and PTGS2 were also obtained in the endometrium on D6.5e by immunohistochemistry. In the decidual cells induced by medroxyprogesterone and 2-O-dibutyryl-cAMP, the rhythmic expression levels of clock genes were attenuated, while Ptgs2 transcription was induced. These results indicate that decidualization causes the attenuation of clock genes and the induction of Ptgs2. Furthermore, in the experiment of Bmal1-siRNA, the rhythmic expression of clock genes and Ptgs2 was attenuated by the siRNA. The transcript levels of Ptgs2 and PGE2 production were increased by treatment with the REV-ERBα antagonist, suggesting the contribution of the nuclear receptor REV-ERBα to Ptgs2 expression. Moreover, Rev-erbα knockdown enhanced the induction of Ptgs2 transcription and PGE2 production by forskolin. Chromatin immunoprecipitation-PCR analysis revealed that REV-ERBα could directly bind to a proximal RORE site of Ptgs2. Collectively, this study demonstrate...
Source: Physiological Reviews - Category: Physiology Authors: Tags: Am J Physiol Endocrinol Metab Source Type: research