Hormonal Regulation of Uterine Secretion of Prostaglandin F2α during Luteolysis in Ruminants1

Abstract

In recent years, considerable progress has been made in our understanding of the endocrine mechanisms that control the pattern and timing of uterine secretion of prostaglandin F2α (PGF2α) during luteolysis in ruminants. Oxytocin may be important in establishing a pulsatile pattern of secretion. Neurohypophyseal oxytocin appears to be released in a pulsatile fashion and may initiate each episode of PGF2α secretion from the uterus. Uterine PGF2α stimulates release of oxytocin from the corpus luteum. Luteal oxytocin further stimulates secretion of PGF2α from the uterus and may induce a transient refractoriness of the uterus to subsequent stimulation with oxytocin. Uterine refractoriness subsides after approximately 6 h. A similar desensitization phenomenon occurs in response to PGF2α at the level of the corpus luteum. Together, uterine and luteal refractoriness may account for the interval between pulses of PGF2α observed during luteolysis. Uterine secretory responsiveness to oxytocin increases at luteolysis, when endogenous, pulsatile secretion of PGF2α normally begins. Thus, the acquisition by the uterus of responsiveness to oxytocin may determine when endogenous secretion of PGF2α occurs during the estrous cycle. Uterine secretory responsiveness to oxytocin develops slowly, in the presence of progesterone. Progesterone exerts two types of effects that contribute to the regulation of PGF2α secretion. First, prolonged exposure to progesterone appears to promote uterine accumulation of arachidonic acid, prostaglandin endoperoxide synthase, and other substances needed for synthesis of PGF2α. Second, progesterone exerts a suppressive effect on secretion, which wanes after prolonged exposure. Together, these effects of progesterone ensure that PGF2α is secreted only at the appropriate time to induce luteolysis.Estradiol has a number of effects that may contribute to the regulation of uterine PGF2α secretion. It has direct effects on the uterus that maximize its responsiveness to oxytocin and may modulate pulsatile secretion of neurohypophyseal oxytocin. These endocrine interactions result in a characteristic pattern of PGF2α secretion from the uterus. The first pulses of PGF2α are relatively low in magnitude. These pulses probably initiate luteal regression. Once luteolysis begins, pulse magnitude increases, perhaps because of changes in concentrations of progesterone and estradiol associated with luteal regression. These high magnitude pulses may complete the luteolytic process.