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

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, pro-ACTH 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.(ABSTRACT TRUNCATED AT 250 WORDS)