Rhythmic gene expression in pituitary depends on heterologous sensitization by the neurohormone melatonin.
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.
von Gall
Charlotte
C
Institute of Anatomy II, Johann Wolfgang Goethe-University, Theodor-Stern-Kai 7, D-60590 Frankfurt, Germany.
Garabette
Martine L
ML
Kell
Christian A
CA
Frenzel
Sascha
S
Dehghani
Faramarz
F
Schumm-Draeger
Petra-Maria
PM
Weaver
David R
DR
Korf
Horst-Werner
HW
Hastings
Michael H
MH
Stehle
Jörg H
JH
D019830:Adenosine-5'-(N-ethylcarboxamide) / Q000494:pharmacology; D000818:Animals; D001683:Biological Clocks / Q000502:physiology*; D018797:Cell Cycle Proteins; D002940:Circadian Rhythm / Q000502:physiology; D006224:Cricetinae; D000242:Cyclic AMP / Q000378:metabolism; D017362:Cyclic AMP Response Element-Binding Protein / Q000378:metabolism; D005786:Gene Expression Regulation / Q000502:physiology*; D017403:In Situ Hybridization; D066298:In Vitro Techniques; D008297:Male; D008550:Melatonin / Q000378:metabolism*; D051379:Mice; D008809:Mice, Inbred C3H; D009474:Neurons / Q000187:drug effects / Q000378:metabolism; D009687:Nuclear Proteins / Q000235:genetics / Q000378:metabolism*; D056950:Period Circadian Proteins; D017111:Phodopus; D010870:Pineal Gland / Q000601:surgery; D010904:Pituitary Gland, Posterior / Q000166:cytology / Q000502:physiology*; D043704:Receptor, Adenosine A2B; D011956:Receptors, Cell Surface / Q000378:metabolism; D018160:Receptors, Cytoplasmic and Nuclear / Q000378:metabolism; D044094:Receptors, Melatonin; D018047:Receptors, Purinergic P1 / Q000378:metabolism*; D015398:Signal Transduction / Q000502:physiology
D018797:Cell Cycle Proteins; D017362:Cyclic AMP Response Element-Binding Protein; D009687:Nuclear Proteins; C539023:Per1 protein, mouse; D056950:Period Circadian Proteins; D043704:Receptor, Adenosine A2B; D011956:Receptors, Cell Surface; D018160:Receptors, Cytoplasmic and Nuclear; D044094:Receptors, Melatonin; D018047:Receptors, Purinergic P1; D019830:Adenosine-5'-(N-ethylcarboxamide); D000242:Cyclic AMP; D008550:Melatonin