ONTOGENY OF BASAL AND REGULATED PROOPIOMELANOCORTIN-DERIVED PEPTIDE SECRETION FROM FETAL AND NEONATAL PITUITARY INTERMEDIATE LOBE CELLS - MELANOTROPHS EXHIBIT TRANSIENT GLUCOCORTICOID RESPONSES DURING DEVELOPMENT

Proopiomelanocortin (POMC)-producing cells comprise nearly 100% of the adult rat intermediate lobe (IL) hormone-producing cells. Secretion b y these cells in the adult is primarily under negative regulation by d opamine. Although the POMC-derived peptide LU-MSH has been detected in plasma of fetal rats, the secretory capability of fetal melanotrophs has not yet been examined directly. Here we have used the reverse hemo lytic plaque assay to assess, at the single-cell level, basal and regu lated release by melanotrophs from fetal and early postnatal ages. Bas al secretion was detected at the earliest age examined [Embryonic Day 17.5 (e17.5)], but CRH (10(-8) M) stimulated secretion was not observe d until e19.5. As development preceded, CRH increased both individual plaque sizes and the percentage of melanotrophs stimulated to secrete. An unexpected, transient inhibition of CRH stimulated release from me lanotrophs by dexamethasone (DEX, 10(-6) M) was observed from e19.5-p2 (postnatal Day 2). By p3, however, DEX no longer inhibited melanotrop h secretion while inhibition of CRH-stimulated release from p3 cortico trophs was readily detected. The dopamine agonist ergocryptine (ERG, 1 0(-6) M) inhibited basal secretion from melanotrophs, but not corticot rophs, at all ages examined. Taken together, these results indicate th at melanotrophs undergo a maturation process in which they are initial ly nonresponsive to CRH, next possess functional CRH and steroid recep tors, and finally, undergo functional uncoupling of steroid receptors which characterizes the adult IL. The loss of steroid-mediated inhibit ion of stimulated secretion parallels the arrival of catecholaminergic input into the IL. In contrast, the early response of melanotrophs to dopaminergic agonists, which can be detected 1 week prior to arrival of catecholaminergic fibers into the neurointermediate lobe, appears t o be an intrinsic feature of these cells that is never present in cort icotrophs. (C) 1996 Academic Press, Inc.