Auto-amplification system in prostaglandin F2α production by endometrium for initiating and progressing luteolysis in mares

In many mammals, including the horse, prostaglandin F2a (PGF) secreted from the endometrium is the major luteolysin. When exogenous PGF is administered to induce luteolysis, the effective dose of PGF is lower in horses than in cattle. The reason why a low dose of PGF is successful in horses is not clear. We have hypothesized that a local autoamplification system of PGF production by the equine endometrium plays a role in inducing luteolysis following administration of a low dose of PGF. To test this hypothesis, we carried out the following in vivo and in vitro studies. In Experiment 1, mares (n1⁄46) at the mid-luteal stage were injected i.m. with 1.0 ml PGF analog (PGFa; cloprostenol 250 mg/ml) and blood samples from the jugular vein were collected frequently at fixed intervals. Progesterone and PGF metabolite (PGFM) concentrations in blood plasma were measured by enzyme immunoassay. Cloprostenol did not show a cross-reaction with PGFM in our assay system. Progesterone had decreased by 50% at 2 h and by about 90% at 24 h after PGFa administration. PGFM increased, showing a first peak at 45 min, then decreased and again increased to the level of the first peak at 16 h; levels exceeding that of the first peak were then maintained until 72 h after the PGFa administration. In Experiment 2, PGF receptor (PTGFR) mRNA expression in endometrial tissues collected from different stages of the estrous cycle was determined by real-time PCR. PTGFR mRNA expression was higher at the