Ovine endometrium synthesizes and releases platelet-activating factor, which can cause the release of prostaglandin F2 alpha by the uterus in situ.
Explanted endometrial tissue from ovariectomized ewes that had received hormone replacement to mimic the luteal phase released platelet-activating factor (PAF) into medium in vitro. On Day 14, 310.1 (261-2185), and on Day 15, 424.4 (14.1-590.7) pg PAF (median 25th-75th percentile; p > 0.05) was released per 100 mg endometrial tissue after a 20-min incubation. A regulatory and final enzyme in the PAF biosynthetic pathway, lysoPAF:acetyltransferase, was also present with a specific activity of 0.533 +/- 0.124 pmol acetate/50 micrograms protein/30 min in Day 14 endometrial tissue and 0.810 +/- 0.468 in Day 15 tissue (mean +/- SEM; p > 0.05). PAF:acetylhydrolase, the metabolic enzyme regulating PAF's half-life, was present in uterine luminal washings, with a specific activity of 3.78 +/- 1.37 nmol acetate released/min/mg protein on Day 14 and 3.41 +/- 0.34 on Day 15 (mean +/- SEM; p > 0.05). Intrauterine infusion of 50-400 micrograms PAF caused a dose-dependent release of prostaglandin (PG) F2 alpha (measured as venous 14-dihydro-15-keto-prostaglandin F2 alpha, PGFM) within 10 min on Days 13-15. The enantiomeric form of PAF was significantly less effective in inducing a rise in venous PGFM. WEB 2086 is reported to be a competitive receptor antagonist for PAF, but a 10-fold excess of WEB 2086 failed to inhibit PAF-induced release of PGFM. It was observed that this dose of WEB alone induced PGFM release, suggesting that in this model this agent may not work as a true competitive antagonist. Repeat challenges at intervals of 0, 90, and 120 min with either 200 micrograms PAF or micrograms oxytocin resulted in a marked tachyphylaxis of response by the third challenge. This desensitization after repeated PAF challenge suggests a specificity of its actions. Infusion of 200 micrograms PAF on Day 14 or 15 at five 60-min intervals resulted in a tachyphylaxis such that by the fourth and fifth challenges, essentially no response was observed. The tachyphylaxis that was induced by four repeat challenges with PAF had no apparent effect on the capacity of the uterus to respond to a fifth challenge with oxytocin. Thus, PAF and oxytocin both caused homologous desensitization of their own capacity to mobilize uterine PGF2 alpha, but PAF did not cause heterologous desensitization of the response to oxytocin. This failure of heterologous desensitization suggests differences in the mechanism of action of the two ligands. Kinetic binding studies showed that PAF did not compete for the oxytocin receptor in vitro. This result demonstrated that the ovine endometrium produces PAF and responds to it by the release of PGF2 alpha in situ. The dynamics of the response elicited by PAF were similar to those of oxytocin, yet the two mediators apparently act separately. PAF may be a modulator of PGF2 alpha release by the ovine uterus during the luteal phase.
Battye
K M
KM
Human Reproduction Unit, Royal North Shore Hospital, St. Leonards, NSW, Australia.
Evans
G
G
O'Neill
C
C
D043203:1-Alkyl-2-acetylglycerophosphocholine Esterase; D000123:Acetyltransferases / Q000378:metabolism; D000818:Animals; D015237:Dinoprost / Q000378:metabolism*; D004717:Endometrium / Q000201:enzymology / Q000378:metabolism*; D015914:Estrogen Replacement Therapy; D005260:Female; D007700:Kinetics; D010052:Ovariectomy; D010121:Oxytocin / Q000378:metabolism; D010741:Phospholipases A / Q000378:metabolism; D010972:Platelet Activating Factor / Q000096:biosynthesis / Q000378:metabolism* / Q000494:pharmacology*; D012756:Sheep / Q000378:metabolism*; D014599:Uterus / Q000187:drug effects / Q000378:metabolism*
D010972:Platelet Activating Factor; D010121:Oxytocin; D015237:Dinoprost; D000123:Acetyltransferases; C046035:1-alkylglycerophosphocholine acetyltransferase; D010741:Phospholipases A; D043203:1-Alkyl-2-acetylglycerophosphocholine Esterase