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Publication : Estrogen-related receptor β deficiency alters body composition and response to restraint stress.

First Author  Byerly MS Year  2013
Journal  BMC Physiol Volume  13
Pages  10 PubMed ID  24053666
Mgi Jnum  J:202687 Mgi Id  MGI:5521233
Doi  10.1186/1472-6793-13-10 Citation  Byerly MS, et al. (2013) Estrogen-related receptor beta deficiency alters body composition and response to restraint stress. BMC Physiol 13:10
abstractText  BACKGROUND: Estrogen-related receptors (ERRs) are orphan nuclear hormone receptors expressed in metabolically active tissues and modulate numerous homeostatic processes. ERRs do not bind the ligand estrogen, but they are able to bind the estrogen response element (ERE) embedded within the ERR response elements (ERREs) to regulate transcription of genes. Previous work has demonstrated that adult mice lacking Errbeta have altered metabolism and meal patterns. To further understand the biological role of Errbeta, we characterized the stress response of mice deficient for one or both alleles of Errbeta. RESULTS: Sox2-Cre:Errbeta mice lack Errbeta expression in all tissues of the developing embryo. Sox2-Cre:Errbeta+/lox heterozygotes were obese, had increased Npy and Agrp gene expression in the arcuate nucleus of the hypothalamus, and secreted more corticosterone in response to stress. In contrast, Sox2-Cre:Errbetalox/lox homozygotes were lean and, despite increased Npy and Agrp gene expression, did not secrete more corticosterone in response to stress. Sox2-Cre:Errbeta+/lox and Sox2-Cre:Errbetalox/lox mice treated with the Errbeta and Errgamma agonist DY131 demonstrated increased corticotropin-releasing hormone (Crh) expression in the paraventricular nucleus of the hypothalamus, although corticosterone levels were not affected. Nes-Cre:Errbetalox/lox mice, which selectively lack Errbeta expression in the nervous system, also demonstrated elevated stress response during an acoustic startle response test and decreased expression of both Crh and corticotropin-releasing hormone receptor 2 (Crhr2). CONCLUSIONS: Loss of Errbeta affects body composition, neuropeptide levels, stress hormones, and centrally-modulated startle responses of mice. These results indicate that Errbeta alters the function of the hypothalamic-pituitary-adrenocortical axis and indicates a role for Errbeta in regulating stress response.
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