Oxytocin receptor gene expression in rat uterus: regulation by ovarian steroids

The present study was designed to investigate a possible role for ovarian s teroids in the regulation of rat uterine oxytocin receptor (OTR) mRNA expre ssion before labour. By using a competitive RT-PCR system, we have previous ly reported that parturition was associated with high levels of uterine OTR mRNA in all the animals examined. On the other hand, near term, some rats showed high OTR nlRNA levels while others did not. We therefore examined th e changes in OTR mRNA expression before and during prostaglandin F-2 alpha (PGF(2 alpha))-induced parturition; a paradigm adopted to reduce the variat ion in the onset of parturition. Injection of PGF(2 alpha) on day 18 of pre gnancy significantly increased OTR mRNA expression in all the rats within 2 4 h of treatment, suggesting that the variation in OTR mRNA levels during s pontaneous parturition may be due to the difference in the timing of the on set of parturition. The increase in OTR mRNA was significantly abolished by injection of the anti-oestrogen compound, tamoxifen. The stimulatory actio n of oestrogen on OTR mRNA expression was then examined in the presence or absence of ovarian factors. Pregnant rats were ovariectomized (OVX) or sham -operated on day 18 of pregnancy and either oestrogen or vehicle was admini stered 6 h after the surgical operation. Oestrogen increased OTR nlRNA sign ificantly in OVX rats 18h after administration compared with sham-operated animals. Moreover, ovariectomy alone on day 18 of pregnancy increased OTR m RNA expression to a level which reached statistical significance 24 h after the operation. In addition, oestrogen treatment increased OTR mRNA levels in OVX virgin rats in which progesterone tubes were implanted for 1 week an d removed 6 h before oestrogen injection. The stimulatory effect of oestrog en was not observed in rats in which the progesterone tubes were implanted for 1 week and not removed. These results suggest that the decline of proge sterone is necessary for the expression of the stimulatory effects of oestr ogen on uterine OTR mRNA.