Oxytocin receptor gene expression in the rat uterus during pregnancy and the estrous cycle and in response to gonadal steroid treatment.

Abstract

It is well established that uterine oxytocin receptors (OTRs) are strongly up-regulated immediately before parturition as well as in response to estrogen (E2) administration. Progesterone (P4), on the other hand, induces a rapid down-regulation. We recently cloned the rat OTR gene and characterized its expression in the rat uterus. In this study, we examined the regulation of OTR messenger RNA (mRNA) levels in rat uterus during pregnancy, the estrous cycle, and in response to gonadal steroid treatment. OTR mRNA levels increased more than 25-fold during gestation: 4.5-fold during the first 21 days and 6-fold within 24 h between day 21 and the onset of parturition. Uterine OTR mRNA levels fell rapidly by 85% within 24 h following parturition. By in situ hybridization, OTR mRNA was localized specifically to the longitudinal and circular layers of the myometrium but was not detected in the endometrium. During the estrous cycle, OTR mRNA levels increased 2-fold between metestrus and proestrus, whereas oxytocin (OT) binding rose more than 10-fold within this same interval. Treatment of ovariectomized rats with E2 lead to a significant increase in both OTR mRNA levels (4.4-fold) and OT binding (< 6-fold). Cotreatment with P4 strongly reduced OT binding by 75% (P < 0.01) but did not significantly affect the E2-induced rise in OTR mRNA (11% decrease, P > 0.1). Our data suggest that the increased expression of OT binding sites observed at the onset of labor and at proestrus is mediated, at least in part, by an E2-induced up-regulation of OTR gene expression. However, it also appears that OTR mRNA levels are not the sole determinants of uterine OT binding. Specifically, P4-mediated OTR down-regulation cannot be explained by an effect on OTR mRNA accumulation and may involve novel mechanisms acting at translational or posttranslational levels.

Extrinsic regulation of cardiomyocyte differentiation of embryonic stem cells

“…Paquin et al [2002] found that RA upregulated OT expression in the fetal heart, which is related to the OT-OT receptor system in P19 cell line. The OT gene promotor contains RA regulatory elements that respond to RA treatments in vivo and ex vivo in cultured cells [Richard and Zingg, 1991;Larcher et al, 1995]. These results suggest that OT is downstream of RA signaling during cardiac differentiation.…”

Changes in Uterine Receptor mRNAs for Oxytocin and Estrogen in the Pseudopregnant Rat

“…This increased uterine responsiveness to oxytocin occurs in parallel with an increase in the number of uterine oxytocin binding sites in rats [3,21], humans [4], rabbits [13,14] and cows [5]. Corresponding increases in uterine oxytocin receptor (OTR) mRNA expression in late pregnancy and parturition have been reported in rats [11,12,19], humans [9], cows [8] and sheep [24,25].Estrogen stimulates the number of uterine oxytocin binding sites [3,20,22] and OTR mRNA expression in ovariectomized (OVX) virgin rats [11,12]. However, injection of estrogen does not stimulate oxytocin receptor mRNA expression in late pregnant rats or progesterone-primed OVX virgin rats, but is effective only after ovariectomy and removal of progesterone, respectively [17].…”

“…3). At the midpoint of PSP, the ERβ mRNA level was similar to that during estrus, indicating that the luteal phase did not affect the ERβ level as it did the ERα mRNA level.While OTR is expressed in the rat uterine myometrium [11], immunohistochemical and in situ hybridization studies have shown that ERα and ERβ expression occur in the Fig. 1.…”

Correlation of Oxytocin (OTR) and Estrogen Receptor (ER) mRNA in the Canine Placenta with the Detected Circulating Levels of Oxytocin and Estrogen during Pregnancy and Parturition

“…Nevertheless, it has been addressed in several species that a narrow relationship exists between estrogen (E), oxytocin (OT) and prostaglandins concentrations, especially towards the transition from pregnancy to parturition. In general, the concentration of uterine oxytocin receptors increases dramatically during gestation, under the influence of the rising estrogen levels (Larcher et al, 1995). Near term, oxytocin binds to its receptors in the decidua stimulating prostaglandin synthesis (Fuchs et al, 1983).…”