Correlation between Oxytocin Receptor Concentration and Responsiveness to Oxytocin in Pregnant Rat Myometrium: Effects of Ovarian Steroids*

Abstract

Marked changes in the uterine binding of oxytocin (OT) occur in rats at the time of parturition or after treatment of ovariectomized rats with estrogen or progesterone. To ascertain that these binding sites represent the biological receptors for OT, we measured the uterine response to OT in various groups of rats in which specific OT binding was also determined. Intact pregnant rats and rats ovariectomized on day 20 of gestation and treated thereafter with oil, estradiol benzoate (5 micrograms/24 h), progesterone (5 mg/24 h), or estradiol and progesterone together had indwelling balloons inserted on day 20 for the recording of uterine response to either iv bolus injections or iv infusions of OT. The uterus was removed 24-48 h after balloon insertion, and OT binding to the particulate fraction as well as nuclear estrogen and cytosolic estrogen receptor concentrations were determined. An inverse correlation (r2 = 0.758) was found between the concentration of OT-binding sites and the threshold dose of OT, and a linear correlation was found between the concentration of binding sites and the uterine activity induced by OT infusion (r2 = 0.852). We conclude, therefore, that the high affinity (Kd, 1-2 nM) binding sites for OT represent the physiological receptors. The concentration of these sites increased progressively during estrogen treatment. Progesterone completely inhibited this estrogen-induced rise. After ovariectomy, there was a modest, but significant, increase in OT receptor concentration which also was prevented by progesterone. The increase in OT receptor concentration was correlated with the estrogen receptor concentration in intact pregnant and estrogen-treated ovariectomized animals, but not in the other groups of animals. The apparent affinity of the receptors for OT was not significantly affected by hormone treatment. We conclude that the concentration of receptors is a major factor controlling the uterine responsiveness to OT, and that the receptor concentrations are regulated by ovarian hormones in a manner related to estrogen receptor activation. In addition, estrogen appeared to enhance the coupling of OT receptor occupancy to the tissue response to OT.

Increase by oestrogen of calcium entry and calcium channel density in uterine smooth muscle

“…The time course of association of nitrendipine binding to PM preparation from untreated rats shown in Figure 3 was very similar to that found earlier in oestrogen-treated rats (Batra, 1985). The binding kinetics, as analysed by Scatchard plot, for both untreated and oestrogen-treated rats are shown in Oestrogen treatment has previously been shown to increase adrenoceptors in the uterine and urethral smooth muscle (Williams & Leflcowitz, 1977;Larsson et al, 1984), oxytocin receptors in the uterus (Fuchs et al, 1983) and muscarinic cholinoceptors in the urinary bladder (Levin et al, 1980). The data of the present study show for the first time that oestrogen also increases the density of membrane calcium channels.…”

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

“…In the uterus, the near-term myometrium is extremely sensitive to oxytocin. 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].…”

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

“…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). In dogs, Gram et al (2014) reported that OTR is involved in the prepartum release of prostaglandins, as a significant increase in the expression of OTR was observed at prepartum luteolysis.…”