Micro-RNAs in the parathyroid: a new portal in understanding secondary hyperparathyroidism.

Abstract

Micro-RNAs (miRNAs) are important to the function of many cells including endocrine systems. We present the reported changes in miRNA profiles in parathyroid adenomas and carcinomas. We review the essential roles of parathyroid miRNAs to the response of the parathyroid to hypocalcemia and uremia. miRNA profiling in parathyroid adenomas and carcinomas revealed alterations in their miRNA expression. To study the function of miRNAs in the parathyroid, mice with parathyroid-specific deletion of dicer, the enzyme essential for miRNA maturation, were studied. Remarkably, the parathyroid-Dicer mice failed to increase serum parathyroid hormone (PTH) after acute hypocalcemia and in parathyroid organ cultures. Moreover, the parathyroid-Dicer mice had an impaired increase in serum PTH, PTH mRNA and parathyroid cell proliferation after both chronic hypocalcemia and uremia. In contrast, the response of the parathyroid- Dicer mice to hypercalcemia and a calcimimetic was intact. The stimulation of the parathyroid by hypocalcemia and uremia is miRNA dependent, as opposed to suppression of the parathyroid by hypercalcemia or a calcimimetic that is miRNA independent. miRNAs are essential for the generation of experimental secondary hyperparathyroidism and may be novel targets for its management in chronic kidney disease patients.