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Minerva Center for Calcium and Bone Metabolism, Nephrology and Hypertension Services, Hadassah University Hospital, Jerusalem, Israel 91120
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 cis sequence in the PTH mRNA 3'-untranslated region, thereby determining the stability of the transcript. PT trans factors and cis elements have been defined.
parathyroid hormone gene expression; posttranscriptional gene regulation; calcium; phosphate; vitamin D; chronic renal failure
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