Impact of Chronic Treatment of Ewes with Estradiol-17β or Progesterone on Oxytocin Receptor Gene Transcription and Ovarian Oxytocin Secretion1

Jul 23, 1998Biology of reproduction

Long-term estradiol or progesterone treatment in female sheep and its effects on oxytocin receptor gene activity and oxytocin release from the ovaries

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Abstract

Mean luteal weights were greater in treated ewes than in controls (p < 0.05).

Endometrial concentrations of oxytocin receptors (OTR) and OTR mRNA were significantly lower in ewes treated with estradiol or progesterone compared to controls.
Progesterone receptor (PR) levels did not differ between groups treated with progesterone and controls.
Prostaglandin F2alpha (PGF2alpha) induced a release of oxytocin (OT) in both control and estradiol-treated ewes, compared to saline-treated ewes.
Exposure to increased concentrations of estradiol or progesterone may lead to down-regulation of OTR in the uterus by suppressing the OTR gene.
Chronic treatment with estradiol during the estrous cycle does not appear to directly affect the ovarian stores of luteal OT.

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Three experiments were conducted, the objectives of which were to 1) examine the effects of exogenous estradiol (E2) and progesterone (P4) on uterine concentrations of oxytocin receptors (OTR) and OTR mRNA, as well as the effect of exogenous P4 on progesterone receptors (PR) during the late luteal phase of the cycle, and 2) ascertain whether chronic E2 treatment of ewes during the cycle would alter prostaglandin F2alpha (PGF2alpha)-induced secretion of luteal oxytocin (OT). In experiment 1, 15 ewes were assigned to a control (n = 5; 2 ml corn oil [CO] s.c. on Days 4-14 of the estrous cycle) and two treatment groups (n = 5 each) receiving either 250 microg E2 s.c. (Days 4-14) or 10 mg P4 s.c. (CO on Days 4-10 and P4 on Days 11-14). Endometria and corpora lutea were removed on Day 15 of the cycle. Mean luteal weights were greater in treated than in control ewes (p < 0.05). Endometrial concentrations of OTR and OTR mRNA were significantly greater in control than in E2- or P4-treated ewes. In experiment 2, five ewes each were treated s.c. with CO or 10 mg P4 on Days 11-14 of the cycle; endometria were then removed on Day 15 for PR assay. Endometrial concentration of PR did not differ between groups. Experiment 3 consisted of 20 ewes assigned to four groups in a 2 x 2 factorial arrangement. Treatment consisted of two dosages of E2 (0 or 250 microg/day) in 2 ml CO and two dosages of PGF2alpha analogue (0 or 125 microg Estrumate). All ewes were injected s.c. with E2 or CO for 11 days as described for experiment 1. On Day 15, all ewes received an i.v. injection of PGF2alpha or saline (Time 0); then jugular blood was collected at frequent intervals for analysis of serum concentrations of OT. PGF2alpha induced a release of OT in control and E2-treated ewes (p < 0.05) compared to the value in saline-treated ewes. Collectively, these data suggest that in cycling ewes, exposure of the uterus to increased concentrations of E2 or P4 causes down-regulation of OTR as a consequence of suppression of the OTR gene. Chronic E2 treatment of ewes during the cycle does not act directly on the ovary to alter the stores of luteal OT.

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Impact of Chronic Treatment of Ewes with Estradiol-17β or Progesterone on Oxytocin Receptor Gene Transcription and Ovarian Oxytocin Secretion1

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