Oxytocin-Stimulated Release of Prostaglandin F_2αfrom Ovine Endometriumin Vitro: Correlation with Estrous Cycle and Oxytocin-Receptor Binding1¹

Abstract

Endometrial and myometrial tissues, obtained from Merino ewes on 5 different days of the estrous cycle, were incubated at 37 C in 30 ml of gassed (95% O2:5% CO2) Krebs-bicarbonate buffer containing, 0, 10, 100 or 1,000 muU/ml oxytocin. Aliquots of the medium were removed at 10 min intervals and examined for prostaglandin F2alpha (PGF2alpha) content by radioimmunoassay. Fresh-frozen (-70 C) samples of endometrial and myometrial tissue were homogenized in Tyrode's solution. Particulate fractions from each tissue, sedimenting between 1,000 X g for 10 min and 165,000 X g for 30 min, were prepared and assayed for [3H]oxytocin-binding activity. Endometrium incubated in vitro released PGF2alpha spontaneously and oxytocin enhanced this release in a dose-dependent manner. The degree of enhancement with low doses of oxytocin appeared to increase as estrus approached, reaching a maximum on the day of estrus. High-affinity binding sites (Kd = 5 to 7 X 10(-10) M) were found in both myometrium and endometrium. The number of high-affinity sites rose to a peak at estrus in both tissues but the binding capacity of endometrium was twice that of the myometrium at this time. Although both tissues released PGF2alpha during incubation, oxytocin enhanced release from endometrial tissue only. The results suggest that (i) the endometrium is a target for oxytocin, (ii) synthesis of PGF2alpha by the uterus may involve interaction between oxytocin and its endometrial receptors and (iii) ovarian steroids may influence uterine PG synthesis by regulating the availability of these receptors.

Relationship between endometrial oxytocin receptors and oxytocin-induced prostaglandin F2 release during the oestrous cycle and early pregnancy in pony mares

“…These findings implicate the uterus as the main source of the stimulus for oxytocin and PGF2(1 release, and are in agreement with the failure of many authors to observe oxytocin release during cervical dilatation or massage in humans (Sala et al, 1965), rabbits (Fuchs et al, 1965), sheep (Peeters and Houvenaghel, 1973), rats (Dreifuss et al, 1976) and cows (Cooper and Foote, 1986). Vaginal distension, however, was found to be a stimulus for oxytocin release in goats and sheep (Roberts, 1971 (Cooper and Foote, 1986) or rabbits (Fuchs et al, 1965), and in rats only under deep anaesthesia (Dreifuss et al, 1976 (Fuchs et al, 1981), sheep (Roberts et al, 1976;Sheldrick and Flint, 1985), cows (Mirando el al, 1993;Fuchs et al, 1996), rabbits (Small el al, 1978) and guinea-pigs (Leaver and Seawright, 1982). (Neely el al, 1979b;Vernon et al, 1981;Douglas and Ginther, 1982 (Betteridge et al, 1985).…”

Role of the uterus in early regression of corpora lutea induced by the ram effect in seasonally anoestrous Barbarine ewes

“…This release is correlated to oxytocin receptor concentrations in the endometrium (Flint et al, 1990). Maximum concentrations occur during oestrus, and are lower, relatively, 4 to 5 days earlier or later (Roberts et al, 1976;Sheldrick and Flint, 1985). During oestrus, plasma concentrations of progesterone are minimal whereas oestradiol concentrations are maximal, suggesting that oxytocin receptor synthesis is inhibited by progesterone (Hunter et al, 1989;Vallet et al, 1990) and increased by oestradiol (Hixon and Flint, 1987).…”

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

“…Oxytocin administered early in the luteal phase of the oestrous cycle causes luteolysis in cattle (Armstrong & Hansel, 1959) and goats (Cooke & Knifton, 1981), and some degree of luteal regression in sheep (Milne, 1963;Dobrowolski, 1973;Hatjiminaglou, Alifakiotis & Zervas, 1979), probably through a stimulatory effect on uterine prostaglandin (PG) F-2a secretion (Hansel & Wagner, 1960;Sharma & Fitzpatrick, 1974;Mitchell, Flint & Turnbull, 1975;Roberts, McCracken, Gavagan & Soloff, 1976). Episodes of secretion of PGF-2a occur simultaneously with those of oxytocin (Flint & Sheldrick, 1983) or oxytocin neurophysin (Fairclough et al, 1980) at luteal regression and both active and passive immunization against oxytocin lead to a delay in luteolysis (Sheldrick, Mitchell & Flint, 1980;Schams, Prokopp & Barth, 1983).…”

“…Levels of oxytocin receptor increase at luteal regression in both myometrium and endometrium (Roberts et al, 1976;, and there is a parallel increase in uterine sensitivity in terms of both contractility (McCracken, Schramm & Okulicz, 1984) and PGF-2a secretion (Roberts et al, 1976).…”