title: 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.
abstract: Androstenedione treatment of pregnant monkeys at 0.8 of gestation reproduces endocrine, biophysical, and biochemical changes similar to those measured during spontaneous, term labor in the pregnant monkey. In the pregnant baboon, the spontaneous onset of labor at term has been attributed to a forward shift in the nocturnal estradiol surge relative to that of progesterone in maternal plasma. This study investigated whether androstenedione treatment of the pregnant baboon at 0.7-0.8 of gestation promotes a premature forward shift in the nocturnal surge of maternal plasma estradiol relative to progesterone and whether this shift is associated with premature increases in nocturnal myometrial activity. Eight pregnant baboons were prepared surgically under general anesthesia with vascular catheters and myometrial electromyogram electrodes between 121 and 139 days of gestation (term is ca. 185 days). Catheters were maintained patent by continuous infusion of heparinized saline from the time of surgery until one of two treatments began following at least 9 days of postoperative recovery. In four baboons (Group I), the saline administration was replaced by a continuous infusion of 10% intralipid vehicle during Day 1 of the experimental protocol. During Day 2 and Day 3, the intralipid infusion was switched for a continuous infusion of androstenedione dissolved in intralipid set at a low (0.8 mg x kg(-1) x h(-1)) and at a high (1.6 mg x kg(-1) x h(-1)) dose, each delivered for 24 h. The other four 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 x kg(-1) x h(-1) for 24 h before the low and the high dose of androstenedione. In each baboon, during each experimental day, maternal arterial blood samples (1 ml) 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 via RIA. Myometrial contractions were counted during each night-time period of the experimental protocol. All pregnant baboons demonstrated increases in maternal plasma estradiol and progesterone concentrations at night-time. Androstenedione had a dose-dependent effect in elevating day-time maternal plasma estradiol concentrations and in promoting a forward shift in the nocturnal surge of maternal plasma estradiol without affecting the nocturnal progesterone profile in maternal plasma. Maternal treatment with androstenedione also led to an increase in nocturnal myometrial contraction activity. We 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 shift is associated with an increase in nocturnal myometrial contraction activity, in a similar way to that measured during spontaneous onset of labor at term in this species.
authors.affiliation: The Physiological Laboratory, University of Cambridge, United Kingdom.
authors.forename: D A
authors.initials: DA
authors.lastname: Giussani
authors.forename: S L
authors.initials: SL
authors.lastname: Jenkins
authors.forename: J A
authors.initials: JA
authors.lastname: Winter
authors.forename: J D
authors.initials: JD
authors.lastname: Tame
authors.forename: P W
authors.initials: PW
authors.lastname: Nathanielsz
mesh_terms: D000735:Androstenedione / Q000494:pharmacology*; D000818:Animals; D002940:Circadian Rhythm / Q000502:physiology; D004958:Estradiol / Q000097:blood*; D005217:Fat Emulsions, Intravenous / Q000494:pharmacology; D005260:Female; D010215:Papio / Q000502:physiology*; D011247:Pregnancy; D011374:Progesterone / Q000097:blood / Q000494:pharmacology*; D014590:Uterine Contraction / Q000187:drug effects*
chemical_list: D005217:Fat Emulsions, Intravenous; D000735:Androstenedione; D011374:Progesterone; D004958:Estradiol