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BMC Physiology

, 13:10

Integrative physiology to internal stimuli


BackgroundEstrogen-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 Errβ have altered metabolism and meal patterns. To further understand the biological role of Errβ, we characterized the stress response of mice deficient for one or both alleles of Errβ.

ResultsSox2-Cre:Errβ mice lack Errβ expression in all tissues of the developing embryo. Sox2-Cre:Errβ 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:Errβ homozygotes were lean and, despite increased Npy and Agrp gene expression, did not secrete more corticosterone in response to stress. Sox2-Cre:Errβ and Sox2-Cre:Errβ mice treated with the Errβ and Errγ agonist DY131 demonstrated increased corticotropin-releasing hormone Crh expression in the paraventricular nucleus of the hypothalamus, although corticosterone levels were not affected. Nes-Cre:Errβ mice, which selectively lack Errβ 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.

ConclusionsLoss of Errβ affects body composition, neuropeptide levels, stress hormones, and centrally-modulated startle responses of mice. These results indicate that Errβ alters the function of the hypothalamic-pituitary-adrenocortical axis and indicates a role for Errβ in regulating stress response.

AbbreviationsACTHAdrenocorticotropic hormone

AgrpAgouti-related protein

CrhCorticotropin-releasing hormone

CrhbpCorticotropin releasing hormone binding protein

Crhr2Corticotropin releasing hormone receptor 2

ERREstrogen-related receptor

ERREEstrogen-related receptor response element

HPAHypothalamic-pituitary-adrenal axis

IMIInter meal interval

ISHIn situ hybridization

NpyNeuropeptide Y

PPIPrepulse inhibition


Electronic supplementary materialThe online version of this article doi:10.1186-1472-6793-13-10 contains supplementary material, which is available to authorized users.

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Autor: Mardi S Byerly - Roy D Swanson - G William Wong - Seth Blackshaw


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