Hormonal and related factors affecting the release of prostaglandin F2α from the uterus

Abstract

While evidence is accumulating that prostaglandin F2α (PGF2α) is the uterine luteolytic factor in several sub-primate species, factors controlling the release of PGF2α from the uterus are not fully documented. The present study utilizes two models consisting of either the in situ or the autotransplanted uterus of the sheep. Four factors affecting the release of PGF2α from the uterus are described, (a) Ovarian steroid hormones: Spontaneous peaks of estradiol-17β (E2-17β) occur throughout the estrous cycle but it is not until the time of corpus luteum regression that peaks of PGF2α release from the uterus become associated with peaks of E2-17β secretion. When physiological amounts of E2-17β are infused into the arterial supply of the autotransplanted uterus, PGF2α, is released only late in the luteal phase suggesting that a priming effect of progesterone may also be necessary for PGF2α synthesis, (b) Oxytocin: When physiological amounts of oxytocin are infused into the arterial supply of the in situ uterus, uterine tonus and amplitude of contractions increase immediately and are associated with a simultaneous increase in PGF2α release, an effect which varied with the steroid status of the animal. Indo-methacin inhibits the oxytocin-induced release of PGF2α but not uterine contractions even although infusions of PGF2α alone mimic this effect of oxytocin. It is possible that PGF2α released during oxytocin action may have other important physiological functions such as altering uterine blood flow or changing cervical tone. (c) Mechanical stimulation: When the in situ uterus is mechanically stimulated by massaging it for 10 min, a rapid and sustained release of PGF2α occurs only very early and very late in the cycle suggesting a dependence of this stimulus on the steroid hormone status of the animal. Peripheral blood levels of oxytocin were found to be elevated during massage at certain stages of the cycle, suggesting that at least some of the massage-induced release of PGF2α may be mediated through oxytocin action on the uterus, (d) Bacterial endotoxin: Endotoxin has long been known to cause abortion in women as well as in lower species. Recent studies in pregnant mice have implicated uterine PGF2α as the mediator of the abortifacient action of endotoxin. Minute quantities of endotoxin injected into the arterial supply of the uterus produce a marked and immediate increase in PGF2α release, an effect which is abolished by Indomethacin. These studies at the organ level confirm and extend the evidence that the abortifacient action of endotoxin is mediated via the release of PGF2α from the uterus.In conclusion the response of the uterus to a variety of physiological and pathological stimuli appears to center invariably on the release of PGF2α (and possibly other PGs) and evidence exists that this event is wholly or partially dependent on the endogenous steroid status of the animal.