Androstenedione treatment of pregnant baboons at 0.7-0.8 of gestation promotes a premature forward shift in the nocturnal maternal plasma estradiol surge relative to progesterone and increases myometrial contraction activity

Androstenedione treatment of pregnant monkeys at 0.8 of gestation reproduce s endocrine, biophysical, and biochemical changes similar to those measured during spontaneous, term labor in the pregnant monkey. In the pregnant bab oon, the spontaneous onset of labor at term has been attributed to a forwar d shift in the nocturnal estradiol surge relative to that of progesterone i n maternal plasma. This study investigated whether androstenedione treatmen t of the pregnant baboon at 0.7-0.8 of gestation promotes a premature forwa rd shift in the nocturnal surge of maternal plasma estradiol relative to pr ogesterone and whether this shift is associated with premature increases in nocturnal myometrial activity. Eight pregnant baboons were prepared surgic ally under general anesthesia with Vascular catheters and myometrial electr omyogram electrodes between 121 and 139 days of gestation (term is ca. 185 days). Catheters were maintained patent by continuous infusion of hepariniz ed saline from the time of surgery until one of two treatments began follow ing at least 9 days of postoperative recovery. In four baboons (Group I!, t he saline administration was replaced by a continuous infusion of 10% intra lipid vehicle during Day 1 of the experimental protocol. During Day 2 and D ay 3, the intralipid infusion was switched for a continuous infusion of and rostenedione dissolved in intralipid set at a low (0.8 mg.kg(-1).h(-1)) and at a high (1.6 mg.kg(-1).h(-1)) dose, each delivered for 24 h. The other f our pregnant baboons (Group II) received 10% intralipid vehicle for Days 1, 2, and 3 of the experimental protocol. One baboon from Group I received an additional dose of 0.4 mg.kg(-1).h(-1) for 24 h before the low and the hig h dose of androstenedione. In each baboon, during each experimental day, ma ternal arterial blood samples (1 mi) were taken at 1 h intervals for 12 h, starting 3 h before the onset of darkness in the animal's environment, for measurement of maternal plasma estradiol and progesterone concentrations vi a RIA. Myometrial contractions were counted during each night-time period o f the experimental protocol. All pregnant baboons demonstrated increases in maternal plasma estradiol and progesterone concentrations at night-time. A ndrostenedione had a dose-dependent effect in elevating day-time maternal p lasma estradiol concentrations and in promoting a forward shift in the noct urnal surge of maternal plasma estradiol without affecting the nocturnal pr ogesterone profile in maternal plasma. Maternal treatment with androstenedi one also led to an increase in nocturnal myometrial contraction activity. W e conclude that androstenedione treatment of the pregnant baboon at 0.7-0.8 of gestation promotes a premature forward shift in the nocturnal estradiol surge relative to that of progesterone in maternal plasma and that this sh ift is associated with an increase in nocturnal myometrial contraction acti vity, in a similar way to that measured during spontaneous onset of labor a t term in this species.