Effect of an Oxytocin Antagonist on Prostaglandin F2α Secretion and the Course of Luteolysis in Sows

Abstract

The role of oxytocin (OT) in the regulation of prostaglandin F2 alpha (PGF2 alpha) secretion during luteolysis in gilts was studied using a highly specific OT antagonist (CAP-581). In Experiment 1 gilts on Days 14 to 19 of the oestrous cycle in Latin square design were used, to determine the dose and time of application of OT and CAP. In Group I (n = 6) gilts were treated intravenously with saline or with 10, 20 and 30 IU of OT. Concentrations of the main PGF2 alpha metabolite i.e. 13,14-dihydro-15-keto-prostaglandin F2 alpha (PGFM) were measured in blood samples as uterine response to the treatment. Twenty IU of OT was the most effective to stimulate PGFM release and this dose was used after CAP treatment in gilts of Groups II, III and IV. Gilts of Group II (n = 3) were injected into the uterine horns (UH) with saline (5 ml/horn) or CAP (2 mg, 3 mg and 4 mg; half dose/horn) and OT was injected (i.v.) 30 min thereafter. Any of the CAP doses given into the UH affected PGFM plasma concentrations stimulated by OT. In Group III (n = 4) gilts were infused (i.v.) for 30 min with CAP (9 mg, 14 mg and 18 mg/gilt) followed by 20 IU of OT. All doses of CAP effectively inhibited OT-stimulated PGF2 alpha release, therefore 9 mg was selected for the further studies. Gilts of Group IV (n = 4) received OT 4, 6 and 8 h after CAP to define how long CAP blocks the OT receptors. Concentrations of PGFM increased after any of this period of time. Thus, we concluded that 9 mg of CAP infused every 4 h will effectively block OT receptors. In Experiment 2, gilts (n = 4) received CAP as a 30-min infusion every 4 h on Days 12-20 of the oestrous cycle. Control gilts (n = 3) were infused with saline. CAP infusions diminished the height of PGFM peaks (P < 0.05). Frequency of the PGFM (P < 0.057) and OT (P < 0.082) peaks only tended to be lower in the CAP-treated gilts. Peripheral plasma concentrations of progesterone (P4) and oestradiol-17 beta (E2) and the time of luteolysis initiation as measured by the decrease of P4 concentration were the same in CAP- and saline-treated gilts. The macroscopic studies of the ovaries in gilts revealed lack of differences between groups. We conclude that OT is involved in the secretion of luteolytic PGF2 alpha peaks but its role is limited to controlling their height and frequency. Blocking of OT receptors did not prevent luteolysis in sows.

Novel insights into the mechanisms of pregnancy establishment: regulation of prostaglandin synthesis and signaling in the pig

“…In ewes, luteal OXT acts through endometrial OXT receptors to generate a PGF 2a pulse which in turn stimulates further secretion of OXT as well as inducing functional regression of the CL through inhibiting progesterone synthesis (reviewed in Jenkin (1992)). In the pig, OXT may not be responsible for the initiation of luteolysis but is more likely involved in the control of pulsatile release of PGF 2a , especially the height and frequency of the peaks of this hormone during luteolysis (Kotwica et al 1999). Surprisingly, OXT concentration in the uterine lumen significantly increases on days 12-14 of pregnancy compared with the corresponding days of the estrous cycle (Vallet et al 1998).…”

Oxytocin and tumor necrosis factor α stimulate expression of prostaglandin E2 synthase and secretion of prostaglandin E2 by luminal epithelial cells of the porcine endometrium during early pregnancy

“…Systemic infusions of OXT antagonist between days 12 and 20 of the estrous cycle reduce the amplitude of PGF 2a metabolite (PGFM) pulses, but do not prevent luteolysis (Kotwica et al 1999). In pigs, the neurohypophysis provides a greater amount of circulating OXT than does the CL during the luteal phase, and plasma OXT increases during luteolysis (Kotwica et al 1990).…”

Luteinising hormone receptor kinetic and LH-induced prostaglandin production throughout the oestrous cycle in porcine endometrium

“…In pigs it is suggested that OT can be involved in the secretion of luteolytic PGF2a peaks but its role is limited only to controlling their height and frequency, since PGF 2 (, release and luteolysis in sows was not prevented by blocking the OT receptors [23].…”