Circadian rhythms of calcitonin gene expression in the rat.

Abstract

The daily changes in rat thyroid calcitonin and its specific mRNA concentrations, and the relationship between their dynamics and the plasma levels of calcitonin, calcium and phosphate over a 24-h period were investigated. The circulating calcitonin concentration rose during the daily dark period when plasma calcium and phosphate levels were minimal, indicating that plasma calcitonin rhythm cannot be generated directly by a linear effect of calcium on hormone secretion. Moreover, we established that the expression of the calcitonin gene also exhibited periodic dynamics observable at the pretranslational level: the gland content of hybridizable specific calcitonin RNA displayed daily rhythms; specific RNA levels peaked during the light period and were minimal during the first part of the dark period. Significant changes in thyroid calcitonin concentrations also occurred over a 24-h period. Statistical analyses which distinguished between variations over the 24-h period and residual variations were performed to test the relationships between the various parameters. The daily rhythms of hybridizable RNA, thyroid calcitonin and plasma minerals appeared to be in phase, while the plasma calcitonin concentration displayed variations out of phase with these rhythms. The implication of the correlations observed on the residual variations is discussed in comparison with the temporal relationship between the daily variations. The results fit the hypothesis that hormone production and secretion are self-oscillating processes. Plasma concentrations of calcium and phosphate might play a role in the synchronization of the calcitonin metabolism periodicity.