EFFECT OF CONTINUOUS INFUSION OF OXYTOCIN ON OVARIAN-FUNCTION AND UTERINE OXYTOCIN RECEPTOR CONCENTRATION IN THE CYCLIC EWE

Intact cyclic ewes have been used in experiments designed to examine the mechanism by which uterine oxytocin receptor synthesis is controlled during the oestrous cyclic. Previous experiments have shown that the prostaglandin F2alpha analogue cloprostenol is luteolytic in ewes receiving oxytocin by continuous intra-venous infusion. When ewes receiving oxytocin are given cloprostenol uterine oxytocin receptor concentrations are raised, whereas in animals receiving oxytocin alone, they remain low. To investigate whether inhibition of oxytocin receptor binding activity by oxytocin is either dependent on elevated plasma progesterone concentrations or over-ridden by oestrogens secreted by ovarian follicles maturing as a result of cloprostenol treatment, ewes were given oxytocin by continuous intravenous infusion (3 nmol h-1) between Days 12 and 17 after oestrus and one of the following: no further treatment; cloprostenol [125 mug intramuscularly (i.m.)] on Day 15; progesterone, by subcutaneous implant, from Day 14 with cloprostenol on Day 15; medroxyprogesterone acetate (MPA; 6 mg depot i.m.) on Day 14 followed by cloprostenol on Day 15; or oestradiol-17beta (2-75 mumol i.m.) on Days 14 and 15. Concentrations of oxytocin receptor were measured at autopsy on Day 17 in caruncular endometrium, intercaruncular endometrium and myometrium. Ovarian follicles and corpora lutea were examined to determine the effect of treatment on these tissues. Treatment with oxytocin alone resulted in the maintenance of corpora lutea, reduced follicular development and a low concentration of uterine oxytocin receptor. Cloprostenol initiated luteolysis in oxytocin-treated ewes. This was associated with a high level of oxytocin receptor binding activity in all ewes except those receiving exogenous progesterone. In these animals progesterone concentrations were similar to those seen in ewes receiving oxytocin alone and, although their corpora lutea had regressed in response to the prostaglandin treatment, oxytocin receptor concentrations remained low and follicular development was inhibited. Oestradiol-17beta failed to induce luteolysis, as judged by concentrations of circulating progesterone and luteal weight, follicular development was inhibited in oestradiol-treated ewes and uterine oxytocin receptor concentrations were higher than those in ewes receiving oxytocin alone. These data show that, although down-regulation of the oxytocin receptor by oxytocin is progesterone-dependent, administration of a pharmacological dose of oestradiol-17beta stimulates receptor synthesis in the presence of high concentrations of both progesterone and oxytocin, but it does not cause luteolysis.