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Publication : Phase-dependent resetting of the adrenal clock by ACTH in vitro.

First Author  Yoder JM Year  2014
Journal  Am J Physiol Regul Integr Comp Physiol Volume  306
Issue  6 Pages  R387-93
PubMed ID  24477539 Mgi Jnum  J:208259
Mgi Id  MGI:5562579 Doi  10.1152/ajpregu.00519.2013
Citation  Yoder JM, et al. (2014) Phase-dependent resetting of the adrenal clock by ACTH in vitro. Am J Physiol Regul Integr Comp Physiol 306(6):R387-93
abstractText  The adrenal cortex has a molecular clock that generates circadian rhythms in glucocorticoids, yet how the clock is synchronized to the external environment is unknown. Using mPER2::Luciferase (mPER2Luc) knockin mice, in which luciferase is rhythmically expressed under the control of the mouse Per2 clock gene, we hypothesized that ACTH transmits entrainment signals to the adrenal. Adrenal explants were administered ACTH at different phases of the mPER2Luc rhythm. Treatment with ACTH 1-39 produced a phase delay that was phase-dependent, with a maximum at circadian time (CT)18; ACTH did not alter the period or amplitude of the rhythm. Forskolin produced a parallel response, suggesting that the phase delay was cAMP-mediated. The response to ACTH was concentration-dependent and peptide-specific. Pulse administration (60 min) of ACTH 1-39 also produced phase delays restricted to late CTs. In contrast to ACTH 1-39, other ACTH fragments, including alpha-melanocyte-stimulating hormone, which do not activate the melanocortin 2 (MC2/ACTH) receptor, had no effect. The finding that ACTH in vitro phase delays the adrenal mPER2luc rhythm in a monophasic fashion argues for ACTH as a key resetter, but not the sole entrainer, of the adrenal clock.
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