The Effects of Pulsed Adrenocorticotropini1–24 Administration to One Twin on the Endocrine and Uterine Activity Changes During Twin Pregnancy in Sheep1

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Abstract
To test the hypothesis that systemic endocrine events are of more importance than local intrauterine endocrine changes in the control of myometrial activity at labor, we examined the endocrine changes and development of uterine activity in chronically catheterized twin fetal sheep during administration of adrenocorticotropin 1-24 (ACTH1-24) to one of the twins. Fetal and maternal plasma cortisol, progesterone, estrone, prostaglandin E2 (PGE2) and 13,14-dihydro 15-keto prostaglandin F2.alpha. (PGFM) were measured before and during pulsatile administration of ACTH1-24 (1 .mu.g infused over 15 min, every 2 h; P-ACTH) to one fetus in each of six twin pregnancies until parturition was initiated. In all cases, each fetus was in a separate uterine horn. The same hormone measurements were made in each co-twin that remained untreated. Intrauterine pressure and electromyographic activity of each uterine horn were monitored continuously throughout the study. In ewes pregnant with twins, the onset of active labor occurred after a mean infusion interval of 204.0 .+-. 29.5 h (SEM), which is considerably longer than has been reported for singleton pregnancies. In the P-ACTH-infused twin, birth was preceded by a progressive rise in plasma cortisol beginning 24 h after the start of infusion. This was followed by a later rise in plasma estrone and PGE2, and by a decline in plasma progesterone. In the uninfused twin, delivery was preceded by a small rise in plasma cortisol that was concomitant with a rise in the concentration of cortisol in the maternal circulation. The concentrations of estrone and progesterone in the uninfused twin did not change significantly. In maternal plasma, there was a progressive fall in the concentration of progesterone, and an increase in the concentration of estrone and PGFM before delivery. The frequency of bursts of uterine electromyographic activity, accompanied by rises in intrauterine pressure, increased in the last 24 h before delivery. This increase in activity was of similar magnitude and occurred at the same time in the uterine horn bearing the P-ACTH-infused twin as in the uterine horn occupied by the untreated co-twin. We conclude that P-ACTH administration to one fetus in twin ovine pregnancy results in activation of fetal adrenal function in the infused twin but not in the untreated co-twin. Since labor does not occur until ACTH has been infused for a considerably longer time in twin compared with singleton pregnancies, it is concluded that the uninfused fetus has a protective influence on the pregnancy. An increase in myometrial activity that was characteristic of early labor occurred at the same time in both uterine horns irrespective of the different endocrine changes taking place within each fetus. These observations support the concept that local intrauterine endocrine changes are less important than systemic endocrine events in the control of myometrial activity at the time of delivery in sheep.