Increasing gestational age and cortisol alter the ratio of ACTH precursors:ACTH secreted from the anterior pituitary of the fetal sheep

Abstract

Abstract We have used a perifusion system and slices of the anterior pituitary of the fetal sheep combined with specific immunoradiometric assays to investigate the effect of increasing gestational age and cortisol infusion on the output of ACTH(1–39) and the ACTH precursors, proACTH and pro-opiomelanocortin, from the fetal sheep pituitary. Two slices from each fetal anterior pituitary at 106–113 days (n=3), 120–136 days (n=5) and 140–143 days (n=5) of gestation were used. Slices from each anterior pituitary were perifused with the perifusion buffer for at least 120 min prior to the infusion of cortisol (100 nm) for 30 min or buffer alone (control). The anterior pituitary output (fmol/5 min per mg pituitary) of ACTH(1–39) and the ACTH precursors were measured using specific immunoradiometric assays. There was a significant increase in the anterior pituitary secretion rate of ACTH(1–39) between 120 and 136 days (1·04 ±0·23 fmol/5 min per mg) and between 140 and 143 days of gestation (3·08 ±0·33 fmol/5 min per mg). In contrast, there was no change in the secretory rate of the ACTH precursors between 105 and 143 days of gestation. The ratio of the anterior pituitary output of the ACTH precursors:ACTH(1–39) therefore decreased between 120 and 143 of days gestation from 19·10 ±2·05 to 6·36 ± 0·58. There was no effect of cortisol infusion on the anterior pituitary secretion of either ACTH(1–39) or the ACTH precursors before 116 days of gestation. After 120 days, the anterior pituitary output of ACTH(1–39) was significantly decreased by cortisol with the maximal change (43 ± 7%) occurring 10–15 min after the start of cortisol inclusion in the perifusate. Cortisol also altered the secretion of ACTH precursors. Although there was no significant effect with respect to baseline secretion rates, precursor secretion was elevated at the beginning of perifusion with cortisol, compared with precursor secretion after cortisol. The ratio of the anterior pituitary output of ACTH precursors:ACTH(1–39) increased from basal values of 16 ±4 and 12 ±4 (precortisol infusion) to 48 ± 14 at 15 min after the start and 40 ± 14 at 45 min after the end of the cortisol infusion. The differential effects of increasing gestational age and cortisol infusion on the output of ACTH(1–39) and the ACTH precursors may be explained by a change in the functional populations of corticotrophs in the fetal sheep anterior pituitary. These changes may be important in the stimulation of the fetal adrenal cortex which occurs before delivery. Journal of Endocrinology (1995) 144, 569–576