OXYTOCIN RECEPTOR GENE-EXPRESSION IN THE RAT UTERUS DURING PREGNANCY AND THE ESTROUS-CYCLE AND IN RESPONSE TO GONADAL-STEROID TREATMENT

It is well established that uterine oxytocin receptors (OTRs) are stro ngly up-regulated immediately before parturition as well as in respons e to estrogen (E(2)) administration. Progesterone (P-4), 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 gonada l steroid treatment. OTR mRNA levels increased more than 25-fold durin g gestation: 4.5-fold during the first 21 days and B-fold within 24 h between day 21 and the onset of parturition. Uterine OTR mRNA levels f ell rapidly by 85% within 24 h following parturition. By in situ hybri dization, OTR mRNA was localized specifically to the longitudinal and circular layers of the myometrium but was not detected in the endometr ium. During the estrous cycle, OTR mRNA levels increased 2-fold betwee n metestrus and proestrus, whereas oxytocin (OT) binding rose more tha n 10-fold within this same interval. Treatment of ovariectomized rats with E(2) lead to a significant increase in both OTR mRNA levels (4.4- fold) and OT binding (<6-fold). Cotreatment with P-4 strongly reduced OT binding by 75% (P < 0.01) but did not significantly affect the E(2) -induced rise in OTR mRNA (11% decrease, P > 0.1). Our data suggest th at the increased expression of OT binding sites observed at the onset of labor and at proestrus is mediated, at least in part, by an E(2)-in duced up-regulation of OTR gene expression. However, it also appears t hat OTR mRNA levels are not the sole determinants of uterine OT bindin g. Specifically, P-4-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.