PTH Regulation by Phosphate and miRNAs

From far, clinical and experimental data pointed to phosphate as a modulator of the parathyroid function. However, it has resulted highly difficult to state clearly a mechanism of action for phosphate on PTH secretion. Twenty-five years ago, the physiological constraints associated with the concomitant changes in serum factors related to mineral metabolism occurring in vivo were overcame through in vitro studies with whole parathyroid glands to show a direct effect. This was shown to be post-transcriptional and then, the responsible cis and trans-acting elements were deciphered throughout the next decade. But to find out a specific phosphate sensor in the parathyroid cells has remained quite elusive. Recent data, however, appears to shed new light on the sensing mechanism, which, amazingly, seems to operate at the very core of the regulation of the parathyroid function since it concerns to the calcium sensing receptor (CaSR) itself. This chapter will cover these mechanisms whereby phosphate modulates the secretion of PTH. And it will also cope with the role of microRNAs (miRNAs), perhaps the last guest star mechanism found to regulate PTH secretion. Through interfering RNAs, specific miRNAs can exert a fine-tuning of gene expression and thus might open new therapeutic prospects.