ABSTRACT. Oxytocin receptor (OTR) mRNA levels increase dramatically near term and is potently stimulated by estrogen because increased OTR mRNA levels result from estrogen treatment in ovariectomized rat uterus. In this study, OTR, estrogen receptor (ER) α and ERβ mRNA levels in the rat uterus during the estrous cycle were examined by quantitative RT-PCR. OTR mRNA levels during the estrous cycle began to increase on diestrus (P<0.05, vs value on estrus), reached maximal increase both in the morning (1000-1130 hr) and afternoon (1600-1630 hr) on proestrus (P<0.01, vs metestrus, diestrus and estrus) and then declined on estrus. In contrast ERα mRNA levels began to decrease on diestrus, reached statistical significance both in the morning and the afternoon on proestrus (P<0.01, vs metestrus, diestrus and estrus) and returned to the value of metestrus on estrus. ERβ mRNA levels were low in the morning and the afternoon on proestrus (P<0.01, vs metestrus and estrus) and also returned to metestrus values on estrus. Treatments with estrogen for 3 days significantly decreased both ERα and ERβ mRNA levels. It can be concluded from these results that during the estrous cycle, OTR mRNA levels in rat uterus predominantly increase at proestrus with a decrease in ERα and ERβ mRNA levels, which is probably due to the increased estrogen levels in circulation before ovulation. KEY WORDS: estrogen receptor, estrous cycle, oxytocin receptor, rat.J. Vet. Med. Sci. 65(6): 707-712, 2003 Oxytocin (OT) was initially isolated as a neurohypophysial hormone which stimulates the contraction of the myometrium and myoepithelium to facilitate parturition and milk ejection respectively, and is considered to act on various reproductive functions in the ovary, the uterus or the brain. In the uterus, the near-term myometrium is extremely sensitive to oxytocin and this increased uterine responsiveness to oxytocin occurs in parallel with an increase in the number of uterine oxytocin binding sites in rats [6,40], humans [7], rabbits [22,23] and cows [9]. Corresponding increases in uterine oxytocin receptor (OTR) mRNA expression in late pregnancy and parturition have been reported in cows [12], rats [20,21,31], humans [17] and sheep [50,52].Estrogen stimulates the number of uterine oxytocin binding sites [6,38,41] and OTR mRNA expression in ovariectomized (OVX) virgin rats [20,21]. However, injection of estrogen does not stimulate oxytocin receptor mRNA expression in late pregnant rats or in progesterone-primed OVX virgin rats, but is effective only after ovariectomy and removal of progesterone, respectively [27]. These results suggest that, in addition to the increase in serum estrogen level near term in rats, regulation of the uterine responsiveness to estrogen is important for understanding the role of estrogen in the uterus. The actions of estrogen are mediated through transcription-regulating intracellular estrogen receptors [1,30]. Two types of estrogen receptor (ER), ERα and ERβ have been cloned from human uterus [11] and rat prostate [19] ...