Activation of ovine fetal adrenal function by pulsatile or continuous administration of adrenocorticotropin-(1-24). I. Effects on fetal plasma corticosteroids.

Abstract

ACTH given as a continuous infusion to fetal sheep causes an increase in plasma cortisol concentrations and premature labor. However, the effects on fetal adrenal responsiveness in vivo and the mode of ACTH administration on plasma corticosteroids are unknown. We examined the effects on plasma corticosteroids of giving the same total amount of ACTH to fetal sheep in utero either as pulses (P-ACTH; 66.7 ng/min for 15 min every 2 h) or continuously (C-ACTH; 0.5 micrograms/h) for 72 h. We determined the changes in vivo in fetal adrenal responsiveness during P-ACTH treatment, and we examined the ability of continued P-ACTH administration to induce premature labor. Both modes of ACTH administration led to a significant (P less than 0.05) increase in the fetal plasma cortisol (F) concentration compared with that in saline-treated controls, but C-ACTH resulted in significantly higher (P less than 0.05) F values than P-ACTH treatment. There was a small increase in the F-binding capacity of fetal plasma during both P-ACTH and C-ACTH, but there was no difference in the cortisol-binding capacity between the two treatments. Twenty minutes from the start of P-ACTH, there was an acute elevation in plasma F to values similar to those found with C-ACTH administration. The magnitude of this response rose significantly (P less than 0.05) between days 1-4 of P-ACTH treatment. There was no significant change in fetal plasma corticosterone during either P-ACTH or C-ACTH, resulting in a 4- to 6-fold increase in the plasma F to corticosterone ratio of both groups. In animals in which P-ACTH treatment was continued beyond 72 h, fetal plasma F continued to rise, and premature labor occurred after 99.0 +/- 4.1 (+/- SE) h. Fetal adrenal weights were not significantly different between P-ACTH for 72 or 100 h or C-ACTH for 72 h, although in each of these groups, the glands were heavier than those in control fetuses. We conclude that activation of fetal adrenal function is demonstrable in vivo during P-ACTH administration. This is reflected by selective F hypersecretion and may lead to premature delivery.