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The effect of an intra-luteal injection of the 5-lipoxygenase (5-LO) inhibitor BWA4C (2 mg in 50 microl DMSO) on the secretion of oxytocin (OT) from the corpus luteum in response to a close-arterial infusion of prostaglandin (PG)-F2alpha (5 ng min(-1)) was examined in anaesthetised sheep. Within 30 minutes of administration both basal (pre-infusion) and PGF2alpha-stimulated OT release into the posterior vena cava were significantly (P<0.01) reduced. These results are consistent with the proposition that 5-LO products of arachidonic acid may modulate OT secretion from the ovine corpus luteum.

Increased peripheral plasma concentrations of testosterone were detected in goats on days 13 and 14 of the oestrous cycle (oestrus = day 0), at the onset of luteolysis. Subcutaneous administration of spironolactone (10 mg kg-1 day-1) on days 10 to 19 inhibited the increases in testosterone, delayed luteolysis and suppressed plasma concentrations of 13,14-dihydro-15-keto-prostaglandin F2 alpha and oxytocin. These results suggest that testosterone of follicular or luteal origin, possibly via aromatisation to oestrogens, is needed to expedite luteolysis and induce oestrus in the goat.

On days 13 and 14 after oestrus (day 0) oxytocin and 13,14-dihydro-15-keto-prostaglandin (PG)F2 alpha (PGFM) concentrations were measured in jugular plasma of hysterectomised sheep with or without systemic treatment with the PG cyclo-oxygenase inhibitor indomethacin (4 mg kg-1 three times a day on days 12, 13 and 14 subcutaneously. Pulsatile increases of oxytocin were observed in both untreated and treated sheep with mean (+/- SD) peak heights of 18.4 +/- 9.6 pg ml-1 (n = 11) and 23.5 +/- 9.4 pg ml-1 (n = 8), respectively; these means were not significantly different. Plasma concentrations of PGFM remained consistently low in both groups (under 100 pg ml-1) with no significant peaks observed. The data suggest that PGF2 alpha may not be the only stimulus for the release of luteal oxytocin, or that there may be a contribution by the posterior pituitary to oxytocin secretion during the luteal phase of the ovine oestrous cycle.

Storage of plasma at -30 degrees C, with no prior treatment, resulted in significant (P less than 0.01) reductions in the biological and immunological activities of oxytocin after 10 days and further reductions after 20 days. Acidification with 0.1 N hydrochloric acid, or snap-freezing in solid carbon dioxide-acetone, before storage afforded some protection against these losses and a combination of both treatments preserved the biological and immunological activities for 20 days despite thawing and refreezing after 10 days.

Spontaneous uterine motility and reactivity to intravenous oxytocin were recorded in eight ovariectomised, oestrogen-primed goats before and after oral meclofenamic acid treatment. Spontaneous motility was completely abolished within 50 to 100 min of meclofenamate administration. However, although uterine reactivity to oxytocin was significantly reduced, the sensitivity was not altered. It is suggested that, in the goat, oxytocin has two effects on the uterus: it increases myometrial activity and also stimulates prostaglandin synthesis.

The disappearance of oxytocin from the peripheral circulation of the goat after a single intravenous injection followed a biexponential curve. The mean (+/- SD) half-life, calculated from the slower component of this decline, was 22.3 +/- 0.6 minutes. The volume of the central compartment was about twice the volume of the vascular compartment and the total apparent volume of distribution was more than twice the size of the extracellular compartment.

Removal of corpora lutea from seven goats during late pregnancy (122 to 129 days) resulted in an abrupt decline in uterine venous plasma progesterone concentrations within 10 min and abortion after a mean interval of 29.88 +/- 1.64 (SD) h. Abortion was preceded by a significant increase in uterine venous plasma PGF concentration either before or coincident with palpable cervical softening. Intrauterine, extra-fetal administration of indomethacin, as a single dose, in a further five lutectomised goats significantly prolonged the interval to abortion and delayed both cervical ripening and the increase in plasma PGF.

Increased peripheral plasma concentrations of testosterone were detected at the commencement of luteolysis and at oestrus in sheep. Daily subcutaneous administration of spironolactone (10 mg kg-1) between days 10 and 16 of the oestrous cycle suppressed testosterone secretion and delayed luteolysis and oestrus. In pregnant ewes no increases in testosterone concentrations occurred between days 10 to 16 after mating and luteal regression, monitored by peripheral progesterone concentrations, was inhibited. It is suggested that aromatisation of testosterone to oestrogens is needed for luteolysis in sheep.

Repeated intramuscular injection of 1 mg prostaglandin F2 alpha (PGF2 alpha) during the luteal phase of the oestrous cycle of the goat hastened luteolysis and resulted in rapid increases in jugular concentrations of 13,14-dihydro-15-keto PGF2 alpha (PGFM), the primary metabolite of PGF2 alpha, and of oxytocin; similar injections of PGF2 alpha in indomethacin-treated goats had a reduced effect on PGFM and oxytocin concentrations, and failed to induce luteolysis. The same injections of PGF2 alpha were without effect on PGFM and oxytocin concentrations in ovariectomised goats. The results suggest that exogenous PGF2 alpha, or endogenous PGF2 alpha released at luteolysis, may induce the release of ovarian oxytocin in the goat.

Luteolysis in the goat was characterised by the pulsatile appearance of both oxytocin and 13,14-dihydro-15-keto-prostaglandin F2 alpha (PGFM), the primary pulmonary metabolite of prostaglandin (PG) F2 alpha, in the peripheral circulation. The episodic, surge release of oxytocin was superimposed on declining levels which paralleled the fall in progesterone concentrations. Daily subcutaneous administration of the prostaglandin synthetase inhibitor indomethacin (10 mg kg-1) between days 11 and 16, delayed luteolysis and suppressed both the decline in oxytocin concentrations and the pulsatile appearance of both oxytocin and PGFM in the peripheral circulation. Although there was little evidence of the release of the two hormones being synchronised, the results suggest that PGF2 alpha may stimulate pulsatile oxytocin release at luteolysis.