Rhythmic gene expression in pituitary depends on heterologous sensitization by the neurohormone melatonin

UMMS Affiliation

Department of Neurobiology; Weaver Lab

Publication Date


Document Type



Adenosine-5'-(N-ethylcarboxamide); Animals; Biological Clocks; Cell Cycle Proteins; Circadian Rhythm; Cricetinae; Cyclic AMP; Cyclic AMP Response Element-Binding Protein; Gene Expression Regulation; In Situ Hybridization; Male; Melatonin; Mice; Mice, Inbred C3H; Neurons; Nuclear Proteins; Period Circadian Proteins; Phodopus; Pineal Gland; Pituitary Gland, Posterior; Receptor, Adenosine A2B; Receptors, Cell Surface; Receptors, Cytoplasmic and Nuclear; Receptors, Melatonin; Receptors, Purinergic P1; Signal Transduction


Neuroscience and Neurobiology


In mammals, many daily cycles are driven by a central circadian clock, which is based on the cell-autonomous rhythmic expression of clock genes. It is not clear, however, how peripheral cells are able to interpret the rhythmic signals disseminated from this central oscillator. Here we show that cycling expression of the clock gene Period1 in rodent pituitary cells depends on the heterologous sensitization of the adenosine A2b receptor, which occurs through the nocturnal activation of melatonin mt1 receptors. Eliminating the impact of the neurohormone melatonin simultaneously suppresses the expression of Period1 and evokes an increase in the release of pituitary prolactin. Our findings expose a mechanism by which two convergent signals interact within a temporal dimension to establish high-amplitude, precise and robust cycles of gene expression.

DOI of Published Version



Nat Neurosci. 2002 Mar;5(3):234-8. Link to article on publisher's site

Journal/Book/Conference Title

Nature neuroscience

Related Resources

Link to Article in PubMed

PubMed ID