Melatonin plays a crucial role in the regulation of rhythmic clock gene expression in the mouse pars tuberalis

Abstract

Circadian rhythms in physiology and behavior are driven by a central clock residing within the hypothalamic suprachiasmatic nucleus (SCN). Molecularly, the biological clock is based on the transcriptional/translational feedback loop of clock genes (mPer, mCry, Clock, and Bmal1). Circadian expression of clock genes is not limited to the SCN, but is found in many peripheral tissues. Peripheral rhythms depend on neuroendocrine/neuronal output from the SCN. Melatonin, the hormone of darkness, represents an important neuroendocrine output of the circadian clock. The hypophyseal pars tuberalis (PT) is one of the main target regions for melatonin. The aim of the study was to test whether mPer, mCry, Clock, and Bmal1 are rhythmically expressed in the mouse PT and how the absence of melatonin receptors affects clock gene expression. We analyzed clock gene expression by in situ hybridization and compared wild-type (WT), melatonin 1 receptor knockout (MT1 ko), and melatonin 2 receptor knockout (MT2 ko) mice. mPer1, mCry1, Clock, and Bmal1, but not mPer2 and mCry2, were rhythmically expressed in the PT of WT and MT2 ko mice. In the PT of MT1 ko mice, expression of mPer1, mCry1, Clock, and Bmal1 was dramatically reduced. We conclude that melatonin, acting through the MT1 receptor, is an important regulator of rhythmic clock gene expression in the mouse PT.