Platelet-activating factor may act as an endogenous pulse generator for sheep of luteolytic PGF(2 alpha) release

Pulsatile release of uterine prostaglandin F-2 alpha (PGF(2 alpha)) induces luteolysis in ruminants. However, the mechanism(s) that initiates and main tains luteolysis has not been defined, The present study tested the hypothe sis that the endogenous PGF(2 alpha) pulse generator is uterine-derived pla telet-activating factor (PAF). Ovariectomized ewes were given exogenous pro gesterone (P), estradiol (E), or both (P+E, mimicking the normal luteal pha se). Only ewes treated with steroids rei leased PAF into the uterine lumen and had increased PAF: acetylhydrolase activity in the uterine lumen. Stero id treatment also influenced the capacity of the uterus to release PGF(2 al pha) in response to exogenous PAF. PAF infusion did not affect plasma PGF(2 alpha) metabolite (PGFM) levels in control (no steroid treatment) ewes but increased plasma PGFM levels in P+E ewes (P < 0.001) and ewes treated with P or E alone (P < 0.05). Infusion of PAF followed by or coincident with ox ytocin (OT) acted in a synergistic manner to increase plasma PGFM levels. R epeated infusion of PAF into the uterus at 1-h intervals induced tachyphyla xis of the PGFM response to PAF; however, sensitivity of the uterus to PAF returned spontaneously by the 6th h. Interferon-tau (IFN-tau) inhibits puls atile release of PGF(2 alpha) during pregnancy to prevent luteolysis. Exoge nous recombinant ovine IFN-tau (50 mu g) 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 PGF(2 alpha) p ulse-generator: steroid induction of PAF production and uterine responsiven ess to PAF-induced release of PGF; synergistic stimulation of PAF-induced P GF release by OT; inhibition of PAF effects by IFN-tau; and PAF's ability t o induce pulses of PGF with a periodicity during a period of chronic exposu re of the uterus to PAF.