Ontogeny of Basal and Regulated Proopiomelanocortin-Derived Peptide Secretion from Fetal and Neonatal Pituitary Intermediate Lobe Cells: Melanotrophs Exhibit Transient Glucocorticoid Responses during Development

Abstract

Proopiomelanocortin (POMC)-producing cells comprise nearly 100% of the adult rat intermediate lobe (IL) hormone-producing cells. Secretion by these cells in the adult is primarily under negative regulation by dopamine. Although the POMC-derived peptide α-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 hemolytic plaque assay to assess, at the single-cell level, basal and regulated release by melanotrophs from fetal and early postnatal ages. Basal secretion was detected at the earliest age examined [Embryonic Day 17.5 (e17.5)], but CRH (10−8M) stimulated secretion was not observed until e19.5. As development proceded, CRH increased both individual plaque sizes and the percentage of melanotrophs stimulated to secrete. An unexpected, transient inhibition of CRH stimulated release from melanotrophs by dexamethasone (DEX, 10−6M) was observed from e19.5–p2 (postnatal Day 2). By p3, however, DEX no longer inhibited melanotroph secretion while inhibition of CRH-stimulated release from p3 corticotrophs was readily detected. The dopamine agonist ergocryptine (ERG, 10−6M) inhibited basal secretion from melanotrophs, but not corticotrophs, at all ages examined. Taken together, these results indicate that melanotrophs undergo a maturation process in which they are initially nonresponsive to CRH, next possess functional CRH and steroid receptors, and finally, undergo functional uncoupling of steroid receptors which characterizes the adult IL. The loss of steroid-mediated inhibition 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 to be an intrinsic feature of these cells that is never present in corticotrophs.