The disruption of circadian clockwork in differentiating cells from rat reproductive tissues as identified by in vitro real-time monitoring system

Abstract

The circadian clock, regulating hormonal secretion and metabolisms

Up-regulation of Per1 expression by estradiol and progesterone in the rat uterus

“…In addition, other two important up-regulatory elements, the cAMP response element (CRE) and glucocorticoid response element (GRE), have been clearly defined by in vitro studies. In response to various resetting cues (Balsalobre et al 2000b, Tsuchiya et al 2005, Yamamoto et al 2005, Hinoi et al 2006, the CRE-binding protein (CREB) or glucocorticoid receptor (GR) was activated, which, in turn, transactivates the transcription of Per1 in the nucleus by binding to the CRE or GRE respectively (Travnickova-Bendova et al 2002, Yamamoto et al 2005, He et al 2007. It is important to note that both CREB and GR act to induce an acute and robust enhancement of Per1 transcription with a peak at 1 h. In contrast, estrogen and P 4 tend to induce a chronic up-regulation of Per1 expression.…”

“…This finding suggests that there may exist other pathway(s) involved in regulating clock gene expression and resetting or modulating the circadian rhythms in vivo by the humoral cues. In vitro studies using clock gene transgenic cells (He et al 2007,) will help to provide direct evidence of whether E 2 or P 4 could serve to reset the circadian clockwork.…”

Hormonal Regulation of Circadian Pacemaker in Ovary and Uterus

“…On day 4.50, treatment of the stroma cells with dexamethasone caused the generation of circadian Per2-dLuc oscillation. This indicates that GREs in the rat Per2 promoter are functional and transactivate the transcription of the Per2 gene (Travnickova-Bendova et al, 2002;Yamamoto et al, 2004;He et al, 2007b). Although the second oscillation in the stroma cells is delayed compared with that of ovarian cells (He et al, 2007b), the circadian oscillation was obvious, with approximately 24 h per cycle at least during the stage of implantation.…”

“…In rodents and humans, uterine endometrial stroma cells undergo proliferation and differentiation into decidual cells, ultimately leading to the formation of the placenta. We previously described that the rhythmic Per2-dLuc oscillation is not observed in the stroma cells undergoing decidualization induced by medroxyprogesterone acetate plus N6, 2-O-dibutyryl adenosine 3':5'-cyclic monophosphate (He et al, 2007b). Stroma cells isolated from pregnant rats on day 4.50 of gestation are proliferative in culture.…”

“…The circadian clock system may contribute to the progress of follicular development, luteinization and luteolysis, and steroid hormone-induced proliferation and differentiation of uterine cells through fluctuating hormones. Recently, there is a growing body of evidence that circadian clock genes are expressed in reproductive tissues including the ovary and uterus (Johnson et al, 2005;Nakamura et al, 2005;Fahrenkrug et al, 2006;Dolatshad et al, 2006;Karman & Tischkau, 2006;He et al, 2007aHe et al, , 2007bHe et al, , 2007cNakao et al, 2007;Hirata et al, 2009;Sellix & Menaker, 2010;Uchikawa et al, 2011). Many regulatory elements are located at the upstream of clock genes, such as steroid hormone response element half-sites and the adenosine 3',5'-cyclic monophosphate (cAMP) response element site as well as E-box and D-box elements.…”