Regulation of oxytocin receptor concentration in rat uterine explants by estrogen and progesterone

Abstract

Incubation of uterine explants from immature rats with 0.01-100 ng of 17 beta-estradiol/mL resulted in approximately a fivefold increase in the number of oxytocin receptors per milligram of protein in 48 h. This increase was maintained for at least an additional 48 h in the presence of estrogen. When the explants were incubated with 1 microgram progesterone/mL from the outset, the concentration of oxytocin receptors was the same as initial (0 time) levels. The estrogen-induced increase in oxytocin receptor concentration was blocked by incubation with cycloheximide, an inhibitor of protein synthesis. Once increased, however, the concentration of oxytocin receptors exhibited no turnover for at least a 48-h period in the presence of estrogen. The addition of progesterone and estrogen to explants with elevated receptor levels resulted in almost a 60% reduction in oxytocin receptor concentration by 24 h, with no change in affinity of the receptor for oxytocin. The reduction in receptor concentration by progesterone was not prevented by cycloheximide. The progesterone effect may involve inactivation or degradation of oxytocin receptors or activation of substances that are inhibitory to oxytocin binding. The effects of estradiol and progesterone on oxytocin receptor concentration in uterine explants are similar to those seen when the steroids are administered in vivo. The explant system, therefore, should prove useful in clarifying factors and processes that are involved in regulation of oxytocin receptor concentration in the uterus and in the initiation of parturition in the rat.

Continuous infusion of oxytocin prevents induction of uterine oxytocin receptor and blocks luteal regression in cyclic ewes

“…To accommodate this observation while retaining the down-regulation hypothesis it may be postulated that the process of down regulation of the oxytocin receptor requires continued exposure of the uterus to progesterone. The increased turnover of the oxytocin receptor induced by progesterone in expiants of rat uterus in organ culture (Soloff et al, 1983) is consistent with such an effect, but there appear to be no comparable data for the sheep.…”

“…The major rise in oxytocin receptor at oestrus appears to be closely linked to declining levels of progesterone and the induction of the receptor by oestrogen can be blocked by progesterone both in vivo (Nissenson, Flouret & Hechter, 1978) and in vitro (Soloff et al, 1983); there is therefore evidence that such a mechanism might operate. As reviewed above it appears most likely that oxytocin infusion delays luteolysis through an inhibitory action on PGF-2rx secretion; it is possible, therefore, that oxytocin affects prostaglandin synthesis, perhaps by reducing the availability of substrate to the synthetase, as a result of interacting with the relatively low levels of oxytocin receptor in the uterus on Day 13 of the cycle.…”

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].…”

Cigarette smoke extract enhances oxytocin-induced rhythmic contractions of rat and human preterm myometrium

“…However, it remains unclear whether the effects of inhalation of cigarette smoke on the expression of OTR mRNA are a direct action on the myometrium or an indirect action via feto-maternal hormonal conditions influenced by cigarette smoke. This uncertainty is based upon the findings that progesterone decreases the levels of uterine OTR mRNA and protein in pregnant rats (Soloff et al 1983), and estrogen increases the levels of OTR in the rat uterus and in human-cultured myometrial cells (Soloff 1975, Adachi & Oku 1995. Additionally, it has been reported that OTR levels are upregulated through progesterone regression, which occurs during luteolysis in the ewe (Hixon & Flint 1987, Zhang et al 1992.…”