Rhythms in clock proteins in the mouse pars tuberalis depend on MT1 melatonin receptor signalling
Weaver, David R.
Stehle, Jorg H.
von Gall, Charlotte
Document TypeJournal Article
KeywordsARNTL Transcription Factors
Basic Helix-Loop-Helix Transcription Factors
In Situ Hybridization
Nerve Tissue Proteins
Pituitary Gland, Posterior
Receptor, Melatonin, MT1
Neuroscience and Neurobiology
MetadataShow full item record
AbstractMelatonin provides a rhythmic neuroendocrine output, driven by a central circadian clock that encodes information about phase and length of the night. In the hypophyseal pars tuberalis (PT), melatonin is crucial for rhythmic expression of the clock genes mPer1 and mCry1, and melatonin acting in the PT influences prolactin secretion from the pars distalis. To examine further the possibility of a circadian clockwork functioning in the PT, and the impact of melatonin on this tissue, we assessed circadian clock proteins by immunohistochemistry and compared the diurnal expression in the PT of wild type (WT), and MT1 melatonin receptor-deficient (MT1-/-) mice. While in the PT of WT mice mPER1, mPER2, and mCRY1 showed a pronounced rhythm, mCRY2, CLOCK, and BMAL1 were constitutively present. Despite reported differences in maximal levels and timing of mCry1, mPer1, and mPer2 RNAs, the corresponding protein levels peaked simultaneously during late day, suggesting a codependency for their stabilization and/or nuclear entry. MT1-/- mice had reduced levels of mPER1, mCRY1, CLOCK and BMAL1, consistent with the earlier reported reduction in mRNA expression of these clock genes. Surprisingly, mPER2-immunoreaction was constitutively low, although mPer2 was rhythmically expressed in the PT of MT1-/- mice. This suggests that mPER2 is degraded due to the reduced levels of its stabilizing interaction partners mPER1 and mCRY1. The results show that melatonin, acting through the MT1, determines availability of the circadian proteins mPER1, mPER2 and mCRY1 and thus plays a crucial role in regulating rhythmicity in PT cells.
SourceEur J Neurosci. 2005 Dec;22(11):2845-54. Link to article on publisher's site
Permanent Link to this Itemhttp://hdl.handle.net/20.500.14038/38035
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