Effects of Corticotropin-Releasing Hormone (CRH) on Monocyte Function, Mediated by CRH-Receptor Subtype R1 and R2

Abstract

Psychosocial factors have been reported to be independently associated with coronary heart disease (CHD). Though corticotropin-releasing hormone (CRH) is the major hormone activated during adaptive responses to stressful stimuli, the undergoing pathophysiological mechanism related to stress-induced endothelial dysfunction is still poorly understood. This study sought to investigate the effects of extrahypothalamic CRH on monocyte/endothelium adhesion. Second we elucidate the influence of CRH on monocytic endothelin-1 (ET-1) and nitric oxide (NO) release and the receptors involved. Cell adhesion was determined using an adhesion assay, MAC-1 expression by flow cytometry. ET-1/NO release were quantified via ELISA or fluorometrically, monocytic CRH-receptors were confirmed by mRNA. Corticotropin-releasing hormone induced a significant time- and concentration-dependent increase of cell adhesion as well as monocytic MAC-1 expression; endothelial ICAM-1 and VCAM-1 expression was not altered. In addition, corticotropin-releasing hormone significantly increased monocytic ET-1 release whereas nitric oxide release was decreased. The effect was abolished by the selective CRH-receptor antagonist astressin. Our findings support the importance of peripherally circulating corticotropin-releasing hormones, by influencing specific homeostatic properties of monocytes. Our data may provide a novel concept of how specific CRH-receptor antagonists may prevent CRH (stress)-related endothelial dysfunction up to cardiovascular complications.