Endocrinology, Vol 116, 2267-2272, Copyright © 1985 by Endocrine Society

ARTICLES

Modulation by cortisol of adrenocorticotropin-induced activation of adrenal function in fetal sheep

JR Challis, D Huhtanen, C Sprague, BF Mitchell and SJ Lye

We examined the hypothesis that cortisol (F) modulates the activation of adrenal function induced by treating fetal sheep in vivo with pulsatile ACTH (P-ACTH). Chronically catheterized sheep fetuses were infused in utero for 100 h between day 127 and day 131 of pregnancy with P-ACTH; P-ACTH plus metopirone; P-ACTH plus metopirone plus F; P- ACTH plus metopirone plus dexamethasone, or saline (controls). After 100 h, basal and ACTH-stimulated output of 11-desoxycortisol (S), F, and progesterone from collagenase-dispersed fetal adrenal cells was measured. Adrenal cells from fetuses treated with P-ACTH in vivo had significantly greater basal and stimulated (delta) outputs of F and S in vitro than controls. These effects were attenuated in fetuses pretreated with P-ACTH plus metopirone. Concurrent in vivo treatment with ACTH plus metopirone plus F restored basal and delta outputs of F and S to values that were not significantly different from those after P-ACTH alone. In vivo treatment with dexamethasone in addition to P- ACTH plus metopirone significantly raised basal outputs of F and S, but the cells were unresponsive to ACTH in vitro. Basal output of progesterone was significantly greater after in vivo P-ACTH plus metopirone plus dexamethasone, but no treatment raised delta progesterone output over controls. These results support a role for glucocorticoids in modulating ACTH-induced activation of adrenal function in late gestation fetal sheep.

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