| [ Summary ] |
Phosphate retention is known to be an important factor in the development of secondary hyperparathyroidism (2HPT). It is very clear that phosphate restriction prevents the progression of 2HPT both in animal models and clinical investigations. Phosphate retention modulates parathyroid function indirectly by decreasing calcitriol production and hypocalcemia. Recently, it has been demonstrated that high extracellular phosphorus concentrations directly stimulate PTH secretion in vitro. The mechanism is an increase of PTH synthesis by a post-transcriptional mechanism. Phosphorus possibly interferes with the stability of PTHmRNA and synthesis of arachnoid acid which is a potent inhibitor of PTH release. It is well understood that phosphate retention induces parathyroid hyperplasia and phosphate restriction prevents phenomena in uremic animal models. Recent experiments clearly demonstrated that in early stage renal failure p21, which is one of cyclin dependent kinase inhibitors, is overexpressed by phosphate restriction and inhibits parathyroid cell proliferation whereas, phosphate retention stimulates expression of transforming growth factor alpha and induces parathyroid growth. Recently, one of the candidates for phosphate sensors on parathyroid cells was succeeded in cloning. That is Na/Pi co-transporter type1. Expression of the transporter is controlled by calcitriol and dietary phosphate. However, the role of the transporter in uremic states is still unclear. In abnormal parathyroid glands, the sensitivity of phosphates may be disturbed. There are still many points to clarify concerning the mechanisms for controlling parathyroid function by phosphates. |