Stimulation of corticotropin-releasing factor gene expression by FosB in rat hypothalamic 4B cells

Abstract

The Fos- and Jun family proteins are immediate-early gene products, and the Fos/Jun heterodimer, activator protein-1 (AP-1), may be involved in the regulation of corticotropin-releasing factor (CRF) gene expression. FosB is a member of the Fos family proteins that is expressed in the paraventricular nucleus of the hypothalamus upon stress exposure, but it has not been clear whether FosB participates in the regulation of CRF gene expression. This study aimed to explore the effect of the FosB and cJun proteins on CRF gene expression in rat hypothalamic 4B cells. The levels of FosB mRNA and cJun mRNA increased following treatment with forskolin, phorbol-12-myristate-13-acetate (PMA), or A23187 in the hypothalamic cells. Overexpression of FosB or cJun potently increased CRF mRNA levels. Furthermore, downregulation of FosB or cJun suppressed the CRF gene expression induced by forskolin, PMA, or A23187. In addition, the basal CRF mRNA levels were partially reduced by cJun downregulation. These findings suggest that FosB, together with cJun, may mediate CRF gene expression in the hypothalamic cells.