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

Dec 1, 1995Endocrinology

Oxytocin receptor gene activity in the rat uterus during pregnancy, reproductive cycles, and hormone treatments

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Abstract

OTR mRNA levels increased more than 25-fold during gestation in the rat uterus.

OTR mRNA levels rose 4.5-fold during the first 21 days of pregnancy and 6-fold in the 24 hours leading up to parturition.
Following parturition, OTR mRNA levels decreased rapidly by 85% within 24 hours.
In the estrous cycle, OTR mRNA levels increased 2-fold between the metestrus and proestrus phases.
Oxytocin binding rose more than 10-fold during the same interval of the estrous cycle.
Estrogen treatment increased OTR mRNA levels by 4.4-fold, while progesterone treatment reduced oxytocin binding by 75%.
The down-regulation of OTR by progesterone may involve mechanisms beyond OTR mRNA accumulation.

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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.

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

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