title: Plasticity in the adrenocorticotropin-related peptides produced by primary cultures of neonatal rat pituitary.
abstract: Intermediate pituitary lobe cells from newborn rats were maintained in culture to determine the extent to which they continue to exhibit the tissue-specific properties of the newborn and adult intermediate pituitary lobes. At all times examined these cultures contained mostly alpha MSH-sized and corticotropin-like intermediate lobe peptide-sized peptides; the alpha MSH-sized peptides were predominantly diacetyl-ACTH-(1-13)NH2. After 6 days in culture, the intermediate pituitary lobe cells retained the ability to synthesize diacetyl-ACTH-(1-13)NH2. Compared to that of the adult, the newborn anterior pituitary lobe is enriched in high mol wt forms of ACTH-related molecules. Therefore, the ability of newborn anterior pituitary lobe cell cultures to develop the adult processing pattern in culture was investigated. After 6 days in culture, peptides the size of alpha MSH predominated rather than ACTH-(1-39), which is the major form found in the adult. Immunocytochemical studies showed that all cultured newborn corticotropes strongly stained for alpha MSH-related material. The alpha MSH-sized molecules were identified as ACTH-(1-13)NH2 by reverse phase HPLC. In 6-day-old cultures of neonatal anterior pituitary lobes grown in the presence of a synthetic glucocorticoid, dexamethasone, the amount of alpha MSH-sized material was diminished, and instead, precursor forms of the ACTH-related peptides were detected. In biosynthetic labeling experiments, the ratio of newly synthesized ACTH-(1-13)NH2 to ACTH-(1-39) was greatly reduced by treatment of the cells with dexamethasone. The extensive cleavage of ACTH-(1-39) and its regulation by dexamethasone are unique to newborn anterior pituitary lobe corticotropes; such plasticity is not observed in cultures of adult tissue.
authors.affiliation: Department of Neuroscience, Johns Hopkins University, Baltimore, Maryland 21205.
authors.forename: S M
authors.initials: SM
authors.lastname: Sato
authors.forename: R E
authors.initials: RE
authors.lastname: Mains
mesh_terms: D000324:Adrenocorticotropic Hormone / Q000031:analogs & derivatives / Q000096:biosynthesis*; D000818:Animals; D000831:Animals, Newborn; D002478:Cells, Cultured; D003907:Dexamethasone / Q000494:pharmacology; D004723:Endorphins / Q000096:biosynthesis; D009074:Melanocyte-Stimulating Hormones / Q000096:biosynthesis; D010902:Pituitary Gland / Q000187:drug effects / Q000378:metabolism*; D010903:Pituitary Gland, Anterior / Q000378:metabolism; D051381:Rats; D011919:Rats, Inbred Strains
chemical_list: D004723:Endorphins; D003907:Dexamethasone; D000324:Adrenocorticotropic Hormone; D009074:Melanocyte-Stimulating Hormones