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

^a Departments of Animal Sciences and Biochemistry/Biophysics, Oregon State University, Corvallis, Oregon 97331-6702

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 F₂ (PGF₂)-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 µg 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 µg/day) in 2 ml CO and two dosages of PGF₂ analogue (0 or 125 µg 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 PGF₂ or saline (Time 0); then jugular blood was collected at frequent intervals for analysis of serum concentrations of OT. PGF₂ 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.

¹ Technical paper no. 11,220, Oregon Agricultural Experiment Station.

² Correspondence: F. Stormshak, Dept. of Animal Science, Oregon State University, Corvallis, OR 97331-6702. FAX: (541) 737–4174;stormshf{at}ccmail.orst.edu

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