Adrenal responsiveness and the timing of parturition in hypothalamo-pituitary disconnected ovine foetuses with and without constant adrenocorticotrophin infusion

Ovine parturition results from an increase in foetal cortisol secretion in late gestation which is dependant on an intact hypothalamo-pituitary connec tion. The cortisol surge and parturition fails in hypothalamo-pituitary dis connected (HPD) foetuses but, paradoxically, immunoreactive (ir)-ACTH conce ntrations and secretory dynamics appear normal. This study compares the occ urrence and timing of labour, basal ir-ACTH and cortisol concentrations and adrenal responsiveness in HPD foetuses (HPD/ACTH) receiving constant ACTH( (1-24)) infusion (43 ng/h/kg) from surgery (114 +/- 1 days gestational age (GA)) with those of saline-infused HPD or intact foetuses (HPD/SAL and INT/ SAL). HPD/ACTH foetuses initiated labour at 147 +/- 2 days GA, which was no t significantly different from INT/SAL foetuses (149 +/- 1 day GA). HPD/SAL foetuses were killed electively at 146 +/- 3 days GA with no signs of labo ur. Foetal ir-ACTH concentrations in all groups were indistinguishable, but only HPD/ACTH and INT/SAL foetuses had a significant cortisol surge. Adren al responsiveness to ACTH((1-24)) (1 mu g/kg) was greater in HPD/ACTH foetu ses than in HPD/SAL or INT/SAL foetuses at all GAs studied. Adrenal respons iveness in HPD/SAL foetuses exceeded that in INT/SAL foetuses at 120 and 13 0 days GA but did not change with GA. In summary, the basal cortisol and pa rturition defect in HPD foetuses was reversed by low-dose ACTH((1-24)) infu sion. Basal cortisol concentrations were unrelated to adrenal responsivenes s. HPD/SAL foetuses had hyper-responsive adrenals compared to those of INT/ SAL foetuses until 130 days GA, suggesting that the foetal hypothalamus exe rts a negative influence on adrenal cortisol responses before 130 days GA, after which time stimulatory influences predominate.