GCMB and PIN1: regulation of parathyroid function on a transcriptional and post-transcriptional level.

Abstract: The extracellular calcium sensing receptor (CaSR) plays a key role in the maintenance of a narrow range of Ca2+ modulating PTH secretion. Moreover, the PTH levels depend from its mRNA stability, and Prolyn isomerase Pin 1 enzyme seems to be closely involved in the stabilization of PTH mRNA. In Pin1-/- animal model, in fact, increased levels of serum PTH protein and PTH mRNA were found, indicating that Pin1 determines basal PTH expression in vivo. In this scenario, regulation of parathyroid function is mediated at transcriptional and post-transcriptional level. The parathyroid glands are bilateral organs and the early stages of their organogenesis are closely linked with thymus organogenesis. Normal parathyroid development is compromised by reduced levels of the transcription factor GCMB (glial missing homolog), suggesting that its gene might be important in mediating the effects of extracellular calcium on PTH expression and/or secretion in parathyroid cells. GCMB-deficient mice lack parathyroid glands but show normal parathyroid hormone serum levels. Studies on angiogenesis in parathyroid cells showed the co-expression of endothelial progenitor markers and parathyroid specific genes (GCMB, PTH, CaSR), suggesting their potential role of these so-called parathyroid/endothelial cells as progenitors cells.