Central corticotropin releasing hormone receptor 2 may participate in sex differential regulation of cold-evoked eating behavior.

Abstract

Corticotropin-releasing factor (CRF) is an important stress hormone, and because of the different distributions and functions of its receptors, CRF has various effects on the stress response of animals. CRF receptor 2 (CRFR2) is a functional receptor of CRF that may be related to appetite regulation and sex differences. In this study, male and female C57BL/6 mice were exposed to an ambient temperature of 4 °C, and feed intake were determined. Consequently, neuronal excitability, as well as the expression of CRFR2 and related genes in the brain were determined. As a result, 1) there were only significant changes in 2 h feed intake and rectal temperature in males; 2) neuronal excitability was elevated in the paraventricular thalamus (PVT) and paraventricular hypothalamic nucleus (PVH) brain regions of both male and female mice; 3) serum corticosterone and the expression of corticosterone receptors in the PVH were elevated in males but not in females; 4) the activation of the CRFR2 signal in the PVT and PVH brain regions differed by sex: the expression of CRFR2 was upregulated in male mice, and the phosphorylation of protein kinase B (AKT) and cAMP-response element binding protein (CREB) was significantly reduced; and 5) the cold-evoked eating behavior of male mice was abolished when CRFR2 in the PVT was knocked down. In summary, we conclude that male mice are more sensitive to cold stress than are female mice. The CRFR2/AKT/CREB signaling pathway in the PVT and PVH may mediate sex differences in the eating behavior of cold-exposed mice.