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  Impaired glucocorticoid production and response to stress in Arntl-deficient male mice.

Leliavski, A., Shostak, A., Husse, J. L., & Oster, H. (2013). Impaired glucocorticoid production and response to stress in Arntl-deficient male mice. Endocrinology, 155(1), 133-142. doi:10.1210/en.2013-1531.

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Item Permalink: http://hdl.handle.net/11858/00-001M-0000-0015-35CC-9 Version Permalink: http://hdl.handle.net/11858/00-001M-0000-0027-CBA8-5
Genre: Journal Article

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Leliavski, A.1, Author              
Shostak, A.1, Author              
Husse, J. L.2, Author              
Oster, H.1, Author              
Affiliations:
1Research Group of Circadian Rhythms, MPI for biophysical chemistry, Max Planck Society, ou_578594              
2Department of Genes and Behavior, MPI for biophysical chemistry, Max Planck Society, ou_persistent34              

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 Abstract: The basic helix-loop-helix transcription factor Aryl Hydrocarbon Receptor Nuclear Translocator-Like (ARNTL, also known as BMAL1 or MOP3) is a core component of the circadian timing system in mammals, which orchestrates 24-hour rhythms of physiology and behavior. Genetic ablation of Arntl in mice leads to behavioral and physiological arrhythmicity, including loss of circadian baseline regulation of glucocorticoids (GCs). GCs are important downstream regulators of circadian tissue clocks and have essential functions in the physiological adaptation to stress. The role of the clock machinery in the regulation of stress-induced GC release, however, is not well understood. Here we show that already under unstressed conditions Arntl-deficient mice suffer from hypocortisolism with impaired adrenal responsiveness to ACTH and down-regulated transcription of genes involved in cholesterol transport in adrenocortical cells. Under stress they show diminished GC and behavioral responses and develop behavioral resistance to acute and subchronic stressors, as shown using forced swim, tail suspension, and sucrose preference tests. These data suggest that the clock gene Arntl regulates circadian and acute secretion of GCs by the adrenal gland. Arntl disruption, probably via its effect on adrenal clock function, modulates stress axis activity and, thus, may promote resistance to both acute and repeated stress.

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Language(s): eng - English
 Dates: 2013-11-04
 Publication Status: Published online
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 Rev. Method: Peer
 Identifiers: DOI: 10.1210/en.2013-1531
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Title: Endocrinology
Source Genre: Journal
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Pages: - Volume / Issue: 155 (1) Sequence Number: - Start / End Page: 133 - 142 Identifier: -