Coordinate and divergent regulation of corticotropin-releasing factor (CRF) and CRF-binding protein expression in an immortalized amygdalar neuronal cell line

CRF is a 41-amino acid neuropeptide best known for its hypophysiotropic act ions. CRF is widely distributed in the central nervous system in areas beyo nd the hypothalamus. CRF-binding protein (CRF-BP) regulates the bioavailabi lity of CRF, and knowledge of the regulation of CRF-BP synthesis is an inte gral component of understanding the actions of CRF. To better study the reg ulation of CRF and CRF-BP, primary amygdalar cultures were immortalized by transfection with the SV 40 large T antigen. A clonal line that expresses C RF immunoreactivity and messenger RNA was selected. The production of CRF p eptide and message by this line is regulated in a manner indistinguishable from primary cultures. We also observed that the immortalized cells express CRF-BP immunoreactivity and messenger RNA. The expression of both CRF and CRF-BP is positively regulated by forskolin and interleukin-6. Unlike CRF, the expression of CRF-BP message and peptide was increased by phorbol 12-my ristate 13-acetate or dexamethasone. These results demonstrate that the syn thesis of CRF and CRF-BP in this clonal cell line may be regulated in paral lel by some agents but not by others. These data also suggest that dexameth asone may decrease the biological availability of CRF in the amygdala by in creasing the expression of CRF-BP, rather than by decreasing CRF expression .