Molecular mechanisms of secondary hyperparathyroidism

Secondary hyperparathyroidism is a frequent complication of chronic renal f ailure (CRF) and a major factor in the pathogenesis of renal osteodystrophy . A high serum phosphate, decreased levels of serum 1,25(OH)(2)D-3 and the subsequently low serum calcium are the major metabolic abnormalities in CRF , which lead to the secondary hyperparathyroidism. At the level of parathyr oid hormone (PTH) secretion there is insensitivity to the ambient serum cal cium. PTH mRNA levels are increased by a post-transcriptional mechanism tha t involves the binding of PT cytosolic proteins to the PTH mRNA 3'-untransl ated region (UTR). In a dietary model of secondary hyperparathyroidism due to hypocalcemia there is increased binding of parathyroid proteins to the 3 '-UTR and decreased degradation as determined by an in vitro degradation as say. Changes in serum phosphate also dramatically regulate PTH mRNA stabili ty. There is also regulation at the level of PT cell proliferation. PT cell proliferation is increased by experimental hypocalcemia or hyperphosphatem ia and decreased by hypophosphatemia and administered 1,25(OH)(2)D-3. The u nderstanding of the molecular mechanisms involved in the genesis of seconda ry hyperparathyroidism will allow the design of new effective strategies in the management of this troubling condition.