REGULATION OF CORTICOTROPIN-RELEASING FACTOR-BINDING PROTEIN EXPRESSION IN CULTURED RAT ASTROCYTES

The regulation of brain corticotropin-releasing factor (CRF)-binding p rotein (BP), an endogenous modulator of the CRF family of neuropeptide s, 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 exa mined the effects of a variety of signal transduction modulators on CR F-BP expression in cultured astrocytes. In particular, the effect of a gents that stimulate protein kinase A and protein kinase C pathways wa s evaluated. CRF-BP was measured using a ligand immunoradiometric assa y. Forskolin, dibutyryl cyclic AMP and 3-isobutyl-1-methylxanthine tre atment resulted in a dose-dependent increase in CRF-BP levels detected in the medium from astrocytes and neurons. The increase in CRF-BP exp ression was not due to increased cell proliferation as measured by [H- 3]thymidine incorporation. In addition, treatment of the astrocytes wi th phorbol myristate acetate, a protein kinase C activator, caused a r obust increase in CRF-BP levels in the medium. Steroids such as dexame thasone, corticosterone, hydrocortisone and, to a lesser extent, dehyd roepiandosterone inhibited the stimulated release of CRF-BP from astro cytes. These data define a primary role for intracellular messengers i n regulating CRF-BP expression in neurons and astrocytes.