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

Nat Neurosci. 2002 Mar;5(3):234-8. doi: 10.1038/nn806.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Adenosine-5'-(N-ethylcarboxamide) / pharmacology
  • Animals
  • Biological Clocks / physiology*
  • Cell Cycle Proteins
  • Circadian Rhythm / physiology
  • Cricetinae
  • Cyclic AMP / metabolism
  • Cyclic AMP Response Element-Binding Protein / metabolism
  • Gene Expression Regulation / physiology*
  • In Situ Hybridization
  • In Vitro Techniques
  • Male
  • Melatonin / metabolism*
  • Mice
  • Mice, Inbred C3H
  • Neurons / drug effects
  • Neurons / metabolism
  • Nuclear Proteins / genetics
  • Nuclear Proteins / metabolism*
  • Period Circadian Proteins
  • Phodopus
  • Pineal Gland / surgery
  • Pituitary Gland, Posterior / cytology
  • Pituitary Gland, Posterior / physiology*
  • Receptor, Adenosine A2B
  • Receptors, Cell Surface / metabolism
  • Receptors, Cytoplasmic and Nuclear / metabolism
  • Receptors, Melatonin
  • Receptors, Purinergic P1 / metabolism*
  • Signal Transduction / physiology

Substances

  • Cell Cycle Proteins
  • Cyclic AMP Response Element-Binding Protein
  • Nuclear Proteins
  • Per1 protein, mouse
  • Period Circadian Proteins
  • Receptor, Adenosine A2B
  • Receptors, Cell Surface
  • Receptors, Cytoplasmic and Nuclear
  • Receptors, Melatonin
  • Receptors, Purinergic P1
  • Adenosine-5'-(N-ethylcarboxamide)
  • Cyclic AMP
  • Melatonin