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Evidence for an internal and functional circadian clock in rat pituitary cells

Becquet, Denis, Boyer, Bénédicte, Rasolonjanahary, Ramahefarizo, Brue, Thierry, Guillen, Séverine, Moreno, Mathias, Franc, Jean-Louis, François-Bellan, Anne-Marie
Molecular and Cellular Endocrinology 2014 v.382 pp. 888-898
DNA microarrays, circadian rhythm, equations, genes, mice, mutants, physiology, prolactin, rats
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.