Premature birth of live lambs induced by pulsatile infusion of ACTH

This study was designed to investigate the effects of pulsatile infusion of ACTH into ovine fetuses on the endocrine changes that precede parturition, the timing of birth and the subsequent survival of the lamb. Where appropriate, these parameters were compared with fetuses infused with pulses of saline and uninfused normal term fetuses. Ten fetuses received a 15-min infusion of synthetic ACTH(1-24) (79 ng/min) from day 125 (n = 9) or day 126 (n = 1) of gestation. Seven fetuses were born prematurely within 174 +/- 14 h (mean +/- S.E.M.) after the commencement of the infusion, i.e. at 132 +/- 0.6 days, whilst three died in utero at 130-131 days. When born all lambs could breath, walk and suckle. Of the seven premature lambs, four died 2-10 days after parturition but three survived for at least 12 months after birth. Fetuses infused with pulses of ACTH exhibited intermittent but very large increases in plasma ACTH values, with the first pulse, on day 1, increasing ACTH values from 5.1 +/- 1.1 to 140 +/- 31.3 pmol/l (P less than 0.001). At the next sampling time, ACTH values were not significantly different from preinfusion values. A similar plasma ACTH profile was observed on each subsequent day of ACTH treatment. In contrast, fetuses (n = 4) infused with pulses of saline between 125 and 131 days exhibited fetal plasma concentrations of ACTH which ranged between 2 and 12 pmol/l for the majority of the time.(ABSTRACT TRUNCATED AT 250 WORDS)