Overexpression of parathyroid pituitary-specific transcription factor (Pit)-1 in hyperphosphatemia-induced hyperparathyroidism of chronic renal failure rats

Background Hyperphosphatemia in renal failure has been identified as a major role in the pathogenesis of hyperparathyroidism that is independent of changes in serum calcium and 1,25(OH)(2)D(3). The aim of this study was to evaluate the expression of parathyroid Pit-1 in hyperphosphatemia-induced secondary hyperparathyroidism (SHPT) of chronic renal failure (CRF) rats. Methods Wistar rats with CRF induced by 5/6 nephrectomy were ramdomly fed with diet containing 1.2% inorganic phosphate (Pi, high phosphate (HP) group, n=9) or 0.2% Pi (low phosphate (LP) group, n=9) for 10 weeks starting from the fourth week after the surgery. Another 7 nephrectomy rats with HP diet were intraperitoneally injected with phosphonoformic acid (PFA, the specific inhibitor of Pit-1, HP+PFA group) 0.15 g/kg every other day for 10 weeks starting from HP diet. Another 6 HP rats injected with the same amount of normal saline as the control of the HP+PFA group (HP+saline group). At the same time, 9 rats with sham surgery received HP diet as the controls. At the 4th week and 14th week, blood was taken for measurement of serum creatinine (SCr), serum calcium (SCa), serum phosphorus (SPi), 1,25(OH)(2)D(3) and intact parathyroid hormone (iPTH). At the 14th week, two parathroid glands (PTGs) of each rat were removed by microsurgery, one gland for immunohistochemistry analysis of proliferating cell nuclear antigen (PCNA), the other one for detection of Pit-1 by Western blotting, and for the measurement of Pit-1 mRNA and PTH mRNA by real-time quantitative polymerase chain reaction. Results In nephrectomy rats, high dierary phosphate induced a marked increase in serum phosphate, iPTH, PTH mRNA and PCNA parathyroid cells, accompanying Pit-1 and its mRNA in parathyroid gland increased significantly. However, serum Ca and 1,25(OH)(2)D(3) remained unchanged. PEA decreased Pit-1 and its mRNA levels to reduce intact PTH, PTH mRNA and PCNA-positive parathyroid cells. Conclusions Expression of parathyroid Pit-1 in hyperphosphatemia-induced SHPT of CRF rats was upregulated. Pit-1 may mediate the stimulation to parathyroid gland by hyperphosphatemia. Chin Med J 2010;123(12):1566-1570http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcApp=PARTNER_APP&SrcAuth=LinksAMR&KeyUT=WOS:000279754100016&DestLinkType=FullRecord&DestApp=ALL_WOS&UsrCustomerID=8e1609b174ce4e31116a60747a720701Medicine, General & InternalSCI(E)PubMed中国科技核心期刊(ISTIC)1ARTICLE121566-157012