Ovine conceptus secretory proteins and bovine recombinant interferon α1-1 decrease endometrial oxytocin receptor concentrations in cyclic and progesterone-treated ovariectomized ewes
Authors: Vallet J. L. , Lamming G. E. 
Published: December 2008

A series of experiments was performed to determine whether proteins produced by the sheep conceptus (oCSP) during the time of maternal recognition of pregnancy or bovine recombinant interferon α1-1 (brIFN) decrease oxytocin receptor concentrations in the endometrium of cyclic or ovariectomized progesterone-treated ewes. In experiment 1, cyclic ewes received intrauterine infusions of serum proteins (oSP), oCSP or brIFN on days 12, 13 and 14 of the oestrous cycle. Ewes then received an oxytocin challenge (1 μg in 0·9% NaCl), and blood samples were taken just before and every 10 min for 1 h after the challenge; these were measured for 13,14-dihydro-15-ketoprostaglandin F2α (PGFM), the stable metabolite of prostaglandin F2α. Endometrial oxytocin receptor concentrations were then measured. The oCSP and brIFN treatments suppressed both endometrial oxytocin receptor concentrations and oxytocin-induced increases in PGFM concentrations.

In experiment 2, ewes were ovariectomized and then pretreated with a fluorogestone acetate-releasing intravaginal device for 10 days followed by oestradiol (25 μg i.m. twice daily for 2 days). Ewes were then treated with progesterone (10 mg i.m. twice daily for 12 days). Ewes received intrauterine infusions of oSP, oCSP and brIFN on days 10, 11 and 12 of progesterone treatment. On the day after the last progesterone treatment, ewes were challenged with oxytocin and blood samples collected to measure PGFM. Endometrial oxytocin receptors were also measured. Treatment with oCSP, but not brIFN, suppressed endometrial concentrations of oxytocin receptor, and neither oCSP nor brIFN altered oxytocin-induced increases in PGFM concentrations.

In experiment 3, ewes were ovariectomized and pretreated as in experiment 2 and then received progesterone treatment for 6, 8, 10 or 30 days. On the day after the last progesterone treatment, ewes received an oxytocin challenge and blood samples and endometrium were collected as in experiment 1. Endometrial oxytocin receptors increased sharply between days 8 and 10 and remained raised after 30 days of progesterone treatment. Oxytocin-induced PGFM increased between 8 and 10 days of progesterone treatment, but no response to oxytocin was detected after 30 of progesterone treatment.

In experiment 4, ewes were pretreated as in experiment 2 and then treated for 10 days with progesterone and received intrauterine infusions of oCSP, oSP or brIFN placebo control buffer on days 8, 9 and 10. Ewes received oxytocin and blood samples and endometrium were collected as in experiment 1. As in experiment 2, oCSP treatment suppressed oxytocin receptor concentrations but did not affect oxytocin-induced PGFM release.

In experiment 5, ewes were treated with steroid hormones as in experiment 4 and then received intrauterine infusions of either brIFN or oSP on days 8, 9 and 10 of progesterone treatment. The brIFN treatment suppressed oxytocin receptor concentrations but did not suppress oxytocin-induced increases in plasma PGFM.

We concluded from these experiments that (1) treatment of cyclic ewes with either oCSP or brIFN decreases endometrial oxytocin receptor concentrations and oxytocin-induced increases in PGFM and (2) in progesterone-treated ovariectomized ewes, treatment with oCSP and brIFN suppresses endometrial oxytocin receptor concentrations but does not suppress oxytocin-induced increases in PGFM.

Journal of Endocrinology (1991) 131, 475–482