Relaxin-3 regulates corticotropin-releasing factor gene expression in cultured rat hypothalamic 4B cells.

The ancestral insulin/relaxin peptide superfamily member relaxin-3 is an important regulator of food intake and behaviors related to anxiety and motivation. Relaxin family peptide receptor 1 (RXFP1) and RXFP3 are expressed in the rat hypothalamic paraventricular nucleus (PVN). Corticotropin-releasing factor (CRF) is produced in the PVN in response to stressors and promotes adrenocorticotropic hormone secretion from the anterior pituitary. We hypothesized that relaxin-3 directly regulates Crf expression in the hypothalamus and investigated its effect on Crf expression in cultured hypothalamic 4B cells. Relaxin-3 increased Crf mRNA levels and stimulated Crf promoter activity. Both protein kinase A and C pathways contributed to relaxin-3-induced Crf promoter activity. Rxfp1 and Rxfp3 mRNA and their proteins were expressed in cultured hypothalamic 4B cells. Relaxin-3 decreased Rxfp1 mRNA and protein levels and increased Rxfp3 mRNA and protein levels. These results suggested that the action of relaxin-3 in cultured hypothalamic 4B cells may be regulated through both RXFP1 and RXFP3.