The effect of CAG repeat polymorphism in the glucocorticoid receptor on stress responses of mice exposed to water-immersion restraint stress

• Published in: International journal of molecular medicine 2010-03, Vol.25 (3), p.415-420
• Main Authors: Tomita, Masafumi, Katsuyama, Hironobu, Okuyama, Toshiko, Watanabe, Yoko, Hidaka, Kazuo, Otsuki, Takemi, Nata, Masayuki
• Format: Article
• Language: English
• ISSN: 1107-3756; 1791-244X
• DOI: 10.3892/ijmm_00000360

Exposure to stress activates the hypothalamus-pituitary-adrenal (HPA) axis, which is followed by an increase in production of its end product, corticosterone, considered to be the most important glucocorticoid (GC) in rodents. Glucocorticoid receptor (GR) signaling has been suggested as a potential mechanism responsible for the pathogenesis of many clinical disorders. Here, we investigated the involvement of the GR polymorphism in stress response. ICR mice were screened by genomic PCR, bred, and divided into 3 groups according to the GR polymorphism, GRwt/wt, GRwt/Qn, and GRQn/Qn. Mice were exposed to water-immersion restraint stress (WRS), and then examined for gastric mucosal lesions, serum corticosterone, serum cytokines and serum Hsp70 levels. Male mice with GRQn/Qn exhibited a significantly greater gastric lesion index than those with GRwt/wt at 6 h of WRS. Stress-induced corticosterone output achieved peak levels at 3 h, after which it was downregulated. The serum level in the control group was GRwt/wt >GRwt/Qn >GRQn/Qn, whereas the order at 6 h of WRS was reversed, GRQn/Qn >GRwt/Qn >GRwt/wt, suggesting that the GRwt allele responded rapidly to stress. The IL-6 levels of each polymorphic line increased at 3 h and particularly at 6 h. On the contrary, the IL-10 levels in GRwt/wt and GRwt/Qn increased following exposure to WRS, whereas that in GRQn/Qn showed no change. The Hsp70 levels in mice with GRQn allele particularly increased at 6 h of WRS, and the concentration in GRQn/Qn significantly increased as compared to that in GRwt/wt. These results suggest that the GR gene polymorphism has a significant impact on the stress-induced output, including the gastric lesion index, corticosterone, cytokines, and Hsp70 levels in serum. The present study provides insights into the role of GR in individual responses to stress.