Evidence for an internal and functional circadian clock in rat pituitary cells.
In primary cultures of rat pituitary cells and in a pituitary sommatolactotroph cell line (GH4C1), endogenous core-clock- as well as hormone-genes such as prolactin displayed a rhythmic expression pattern, fitted by a sinusoidal equation in which the period value was close to the circadian one. This is consistent with the presence of a functional circadian oscillator in pituitary cells whose importance was ascertained in GH4C1 cell lines stably expressing a dominant negative mutant of BMAL1. In these cells, both endogenous core-clock- and prolactin-genes no more displayed a circadian pattern. Some genes we recently identified as mouse pituitary BMAL1-regulated genes in a DNA-microarray study, lost their circadian pattern in these cells, suggesting that BMAL1 controlled these genes locally in the pituitary. The intra-pituitary circadian oscillator could then play a role in the physiology of the gland that would not be seen anymore as a structure only driven by hypothalamic rhythmic control.
CRN2M, CNRS UMR 7286, Aix-Marseille Université, Marseille, France.
Denis
D
Becquet
CRN2M, CNRS UMR 7286, Aix-Marseille Université, Marseille, France.
Bénédicte
B
Boyer
CRN2M, CNRS UMR 7286, Aix-Marseille Université, Marseille, France.
Ramahefarizo
R
Rasolonjanahary
CRN2M, CNRS UMR 7286, Aix-Marseille Université, Marseille, France.
Thierry
T
Brue
CRN2M, CNRS UMR 7286, Aix-Marseille Université, Marseille, France.
Séverine
S
Guillen
CRN2M, CNRS UMR 7286, Aix-Marseille Université, Marseille, France.
Mathias
M
Moreno
CRN2M, CNRS UMR 7286, Aix-Marseille Université, Marseille, France.
Jean-Louis
JL
Franc
CRN2M, CNRS UMR 7286, Aix-Marseille Université, Marseille, France. Electronic address: anne-marie.francois@univ-amu.fr.
Anne-Marie
AM
François-Bellan
D056930:ARNTL Transcription Factors / Q000235:genetics* / Q000378:metabolism; D000818:Animals; D001683:Biological Clocks / Q000235:genetics*; D002940:Circadian Rhythm / Q000235:genetics; D005786:Gene Expression Regulation; D052682:Lactotrophs / Q000166:cytology / Q000378:metabolism*; D008297:Male; D017440:Photoperiod; D010902:Pituitary Gland / Q000166:cytology / Q000378:metabolism*; D061251:Primary Cell Culture; D011388:Prolactin / Q000235:genetics* / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D019076:Transgenes
D056930:ARNTL Transcription Factors; D011388:Prolactin
Circadian oscillator; Clock-controlled genes; Core-clock genes; GH4C1 cells; Pituitary cells