Platelet-activating factor may act as an endogenous pulse generator for sheep of luteolytic PGF2a release

Chami, O., A. Megevand, T. Ott, F. Bazer, and C. O’Neill. Platelet-activating factor may act as an endogenous pulse generator for sheep of luteolytic PGF2a release. Am. J. Physiol. 276 (Endocrinol. Metab. 39): E783–E792, 1999.— Pulsatile release of uterine prostaglandin F2a (PGF2a) induces luteolysis in ruminants. However, the mechanism(s) that initiates and maintains luteolysis has not been defined. The present study tested the hypothesis that the endogenous PGF2a pulse generator is uterine-derived platelet-activating factor (PAF). Ovariectomized ewes were given exogenous progesterone (P), estradiol (E), or both (P1E, mimicking the normal luteal phase). Only ewes treated with steroids released PAF into the uterine lumen and had increased PAF: acetylhydrolase activity in the uterine lumen. Steroid treatment also influenced the capacity of the uterus to release PGF2a in response to exogenous PAF. PAF infusion did not affect plasma PGF2a metabolite (PGFM) levels in control (no steroid treatment) ewes but increased plasma PGFM levels in P1E ewes (P , 0.001) and ewes treated with P or E alone (P , 0.05). Infusion of PAF followed by or coincident with oxytocin (OT) acted in a synergistic manner to increase plasma PGFM levels. Repeated infusion of PAF into the uterus at 1-h intervals induced tachyphylaxis of the PGFM response to PAF; however, sensitivity of the uterus to PAF returned spontaneously by the 6th h. Interferon-t (IFN-t) inhibits pulsatile release of PGF2a during pregnancy to prevent luteolysis. Exogenous recombinant ovine IFN-t (50 μg) inhibited the uterine response to PAF alone or the combined effects of PAF and OT. These results indicate that uterine PAF fulfills many of the criteria for an endogenous PGF2a pulsegenerator: steroid induction of PAF production and uterine responsiveness to PAF-induced release of PGF; synergistic stimulation of PAF-induced PGF release by OT; inhibition of PAF effects by IFN-t; and PAF’s ability to induce pulses of PGF with a periodicity during a period of chronic exposure of the uterus to PAF.