Induction of Parturition in Sheep by Low Dose Intrafetal Infusion of Synthetic Adrenocorticotropin-(1–24) at 120– 130 Days Gestation*

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Abstract
ACTH infusions into fetal sheep have been extensively used as a method of inducing premature parturition and the investigation of the associated endocrine and maturational changes in the fetus and ewe. Synthetic ACTH [ACTH-(1–24)] has been generally used in doses of 4–10 μg/h to induce parturition. These dose rates greatly exceed calculated endogenous fetal blood production rates for ACTH. The present study was designed to investigate the endocrine changes occurring in fetal and maternal ovine plasma during the induction of premature delivery with continuous infusion of a more physiological dose [1 μg ACTH-(1–24)/h]. The effect of ACTH-(1–24) infusions to the fetus at 120 or 130 days gestation were compared with appropriate gestational age controls. During ACTH-(1–24) infusion, the fetal plasma cortisol concentration in both age groups rose at similar rates. Furthermore, levels at delivery were equal to those observed in normal term fetuses. Where possible, three-parameter exponential curves were fitted to estrone sulfate, estrone, and progesterone concentrations in fetal and maternal plasma. The maternal plasma estrone sulfate concentration rose after 40 h of ACTH-(1–24) infusions. The fetal plasma estrone sulfate concentration rose at 54 h. The fetal to maternal plasma estrone sulfate concentration ratio fell. During ACTH-(1–24) infusion, both maternal and fetal plasma estrone sulfate concentrations were higher than concentrations observed in spontaneous term delivery. Fetal and maternal plasma estrone concentrations rose during ACTH-(1–24) infusion and were similar to those observed at spontaneous term delivery. The maternal plasma progesterone concentration was variable, and although there was a fall in all experimental animals, it was not possible to fit good exponential curves to the plasma profile. We conclude that the fetal sheep adrenal at 120 and 130 days gestation responds well to 1 μg ACTH-(1–24)/h. However, the endocrine changes produced during this infusion differ from those at normal term delivery. The circulating maternal plasma progesterone pool is a poor reflection of placental progesterone metabolism in sheep.