The activation of the hypothalamic-pituitary-adrenal axis in fetal sheep is the primary initiator of parturition; however, this same mechanism has not been proven to be important in primate parturition. To determine if adrenocorticotropic hormone (ACTH) can induce premature parturition in primates, we infused ACTH (0.1 U in 30 min, every 2 hrs; n=7) beginning on day 135 of pregnancy (term=167 days) until delivery occurred. A control group of animals (n=3) received saline vehicle infusions. All animals were surgically instrumented with fetal and maternal vascular and amniotic fluid catheters, fetal ECG and myometrial EMG electrodes. Uterine activity (UA) and fetal ECG were recorded continuously. The results of ACTH and vehicle infusion are listed in the following table (values are mean + SEM) * = P<0.05 (t-test) ACTH vs Vehicle Begin Infusion (day of preg) Onset Nocturnal UA (days) Days to Delivery Delivery (Day of Pregnancy) ACTH (n=6) 135.3 + 0.6 6.3 + 0.8 15.2 + 1.3 149.7 + 1.3 Vehicle (n=3) 135.7 + 1.8 24.7 + 2.7* 27.6 + 3.2* 163.3 + 1.5* One ACTH-treated animal was delivered by cesarean section at 165 days of pregnancy after prolonged labor and dystocia and was excluded from the data set. Mean (+ SEM) maternal and fetal steroid changes in ACTH-treated animals *=P<0.005 (Rank Sum Test) (n=6) Fetal Cortisol (ng/ml) Fetal DHEA-Sulfate (?g/ml) Fetal Androstene-dione (ng/ml) Fetal Estrone (pg/ml) Maternal Estradiol (pg/ml) Baseline 79 + 11 0.4 + .08 0.8 + 0.2 97 + 27 360 + 45 Labor 276 + 48* 6.6 + 3.1* 7.4 + 1.7* 519 + 170* 877 + 187* We conclude that infusion of ACTH into the fetal circulation activates fetal adrenal steroid biosynthesis causing increased secretion of glucocorticoids and androgens leading to increased estrogen and cortisol production and pre-term delivery in rhesus monkeys. FUNDING NIH HD06159, HD18185 PUBLICATIONS None
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