Post-transcriptional Regulation of Parathyroid Hormone Gene Expression in Health and Disease

Abstract

Parathyroid hormone (PTH) determines mineral metabolism and bone strength. Changes in serum calcium are sensed by the parathyroid calcium receptor. Secondary hyperparathyroidism (SHP) due to chronic hypocalcemia or chronic kidney disease (CKD) are characterized by increased serum PTH and PTH mRNA levels and parathyroid cell proliferation. The increase in PTH gene expression by either dietary induced hypocalcemia or CKD is post-transcriptional and mediated by the differential binding of trans acting proteins to a defined cis element in the PTH mRNA 3′-untranslated region (UTR). These protein-PTH mRNA interactions are orchestrated by the peptidylprolyl isomerase Pin1. Using parathyroid specific Dicer1 knock-out (PT-Dicer−/−) mice that have reduced micro-RNA (miRNA) expression specifically in their parathyroids, we showed that miRNA maturation is essential for the increased PTH secretion after both short-term and chronic hypocalcemia in vivo and in vitro, as well as for the SHP of CKD. This chapter discusses the molecular mechanisms that regulate PTH gene expression thereby determining serum PTH levels and mineral metabolism.