LOCAL PARACRINE EFFECTS OF ESTRADIOL ARE CENTRAL TO PARTURITION IN THE RHESUS-MONKEY

The central biochemical mechanisms involved in primate parturition are still unclear. Studies in both humans and nonhuman primates such as t he baboon and rhesus monkey indicate that many factors play a part in the cascade of interactive positive feedforward loops that progressive ly promote parturition: changes in maternal endocrinology, a nocturnal switch in myometrial activity from low amplitude, infrequent contract ures to high amplitude, high frequency contractions (see Fig. 1), dila tion of the cervix and biochemical changes in the fetal membranes that lead to rupture(1). Here we demonstrate that infusion of the aromatas e inhibitor 4-hydroxyandrostenedione (40HA) inhibits conversion of and rogen to estrogen and prevents premature delivery caused by administra tion of androgen to pregnant rhesus monkeys at 0.8 of pregnancy term. 40HA also inhibited the androstenedione induced maternal endocrine and fetal membrane biochemical changes, and alteration of myometrial acti vity patterns. Secondly, peripheral estrogen infusions increased myome trial activity but did not produce preterm delivery or fetal membrane changes. We conclude that paracrine functions of estrogen at its site of production play critical and central roles in delivery in the non-h uman primate.