Effect of surgical isolation of pituitary from hypothalamic influences on corticotroph development in fetal sheep

Abstract

During development, corticotrophs (ACTH‐secreting cells) undergo changes that alter the secretory products they release. In vivo, the ratio of plasma concentrations of ACTH to its biosynthetic precursors (which are ACTH antagonists at adrenals) increases over gestation, and the change is prevented by surgical hypothalamo‐pituitary disconnection (HPD). The present study aimed to determine whether the gestational changes observed in intact and HPD sheep fetuses are mirrored in changes in individual corticotrophs. Pituitaries were harvested from (1) adult sheep and fetuses at 110d gestation (2, term ~ 147d) or at 140d following sham (3) or HPD (4) surgery at 110d. Pituitary sections were simultaneously immunostained for full length POMC, the parent molecule of ACTH, and ACTH(1‐39). The fraction of pituitary cells containing only POMC decreased from 110d (8.8±1.45%) to adulthood (2.8±0.7%), with 140d sham pituitaries indistinguishable from adult, and 140d HPD indistinguishable from 110d. The fractions of cells containing only ACTH(1‐39) or ACTH+POMC were similar in all intact groups, but significantly higher in HPD pituitaries. These results suggest a linear progression over the final third of gestation into adulthood whereby more corticotrophs acquire the capacity to process POMC to ACTH(1‐39). This process is influenced in late gestation by signals from the hypothalamus.