ONTOGENY OF BASAL AND REGULATED SECRETION FROM POMC CELLS OF THE DEVELOPING ANTERIOR LOBE OF THE RAT PITUITARY-GLAND

Proopiomelanocortin (POMC)-producing cells are present in both the ant erior (AL) and intermediate (IL) lobes of the adult rat pituitary. Bot h cell types are derived from a single embryonic rudiment, Rathke's po uch, and synthesize the same hormone precursor, POMC, but differ in th e pattern of precursor processing and regulation of peptide secretion. Here we have used the reverse hemolytic plaque assay to determine the ontogeny of basal and regulated secretion by AL POMC cells. Basal sec retion of beta-endorphin was first observed at Embryonic Day 13.5 (e13 .5), the age when POMC-derived peptides were first detected immunocyto chemically. Peptide secretion stimulated by corticotropin releasing ho rmone (CRH; 10(-8) M) was first detected at e15.5. The CRH-stimulated secretion involved two different components: (1) an increase in the am ount of hormone secreted per cell (increase in plaque size) as well as (2) an increase in the number of plaque-producing cells. The greatest stimulation by CRH was observed at e16.5, a time when AL POMC mRNA le vels increase significantly and when CRH neurons are first detected im munocytochemically in the hypothalamus. CRH-stimulated secretion, but not basal release, was inhibited by preincubation with dexamethasone ( DEX; 10(-6) M) as early as e15.5, while the dopamine agonist ergocrypt ine (ERG; 10(-6) M) did not alter basal or CRH-stimulated release at a ny age studied. These results demonstrate that AL POMC cells are capab le of hormone secretion as early as POMC peptides are first detected i mmunocytochemically and that these cells respond in an adult-like mann er to physiological regulators soon after their initial appearance. Mo reover, these responses remain unaltered during the early postnatal st ress-nonresponsive period, suggesting that deficits at this time must lie at a level other than the corticotroph. Taken together, these resu lts show that AL POMC cells possess functional regulatory receptor sys tems prior to maturation of the hypothalamic-hypophyseal portal system . (C) 1996 Academic Press, Inc.