title: Regulation of corticotropin-releasing factor-binding protein expression in cultured rat astrocytes.
abstract: The regulation of brain corticotropin-releasing factor (CRF)-binding protein (BP), an endogenous modulator of the CRF family of neuropeptides, has been difficult to pursue due to a lack of basal expression in a known cell line or primary cells in vitro. In light of the ability of intracellular factors to modulate neuronal and glial function, we examined the effects of a variety of signal transduction modulators on CRF-BP expression in cultured astrocytes. In particular, the effect of agents that stimulate protein kinase A and protein kinase C pathways was evaluated. CRF-BP was measured using a ligand immunoradiometric assay. Forskolin, dibutyryl cyclic AMP and 3-isobutyl-1-methylxanthine treatment resulted in a dose-dependent increase in CRF-BP levels detected in the medium from astrocytes and neurons. The increase in CRF-BP expression was not due to increased cell proliferation as measured by [3H]thymidine incorporation. In addition, treatment of the astrocytes with phorbol myristate acetate, a protein kinase C activator, caused a robust increase in CRF-BP levels in the medium. Steroids such as dexamethasone, corticosterone, hydrocortisone and, to a lesser extent, dehydroepiandosterone inhibited the stimulated release of CRF-BP from astrocytes. These data define a primary role for intracellular messengers in regulating CRF-BP expression in neurons and astrocytes.
authors.affiliation: Neurocrine Biosciences, Inc., San Diego, California, USA.
authors.forename: D
authors.initials: D
authors.lastname: Maciejewski
authors.forename: P D
authors.initials: PD
authors.lastname: Crowe
authors.forename: E B
authors.initials: EB
authors.lastname: De Souza
authors.forename: D P
authors.initials: DP
authors.lastname: Behan
mesh_terms: D000818:Animals; D001253:Astrocytes / Q000187:drug effects*; D002352:Carrier Proteins / Q000378:metabolism*; D002478:Cells, Cultured; D005576:Colforsin / Q000494:pharmacology; D003346:Corticotropin-Releasing Hormone / Q000378:metabolism*; D000242:Cyclic AMP / Q000494:pharmacology; D051381:Rats
chemical_list: D002352:Carrier Proteins; D005576:Colforsin; D003346:Corticotropin-Releasing Hormone; D000242:Cyclic AMP