Mechanisms of secondary hyperparathyroidism

Small decreases in serum Ca2+and more prolonged increases in serum phosphate (Pi) stimulate the parathyroid (PT) to secrete parathyroid hormone (PTH), and 1,25(OH)2D3 decreases PTH synthesis and secretion. A prolonged decrease in serum Ca2+ and 1,25(OH)2D3, or increase in serum Pi, such as in patients with chronic renal failure, leads to the appropriate secondary increase in serum PTH. This secondary hyperparathyroidism involves increases in PTH gene expression, synthesis, and secretion, and if chronic, to proliferation of the PT cells. Low serum Ca2+ leads to an increase in PTH secretion, PTH mRNA stability, and PT cell proliferation. Pi also regulates the PT in a similar manner. The effect of Ca2+ on the PT is mediated by a membrane Ca2+receptor. 1,25(OH)2D3 decreases PTH gene transcription. Ca2+ and Pi regulate the PTH gene posttranscriptionally by regulating the binding of PT cytosolic proteins, trans factors, to a defined cissequence in the PTH mRNA 3′-untranslated region, thereby determining the sta...