{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,8]],"date-time":"2026-05-08T20:34:36Z","timestamp":1778272476996,"version":"3.51.4"},"reference-count":40,"publisher":"Oxford University Press (OUP)","issue":"12","license":[{"start":{"date-parts":[[2002,12,1]],"date-time":"2002-12-01T00:00:00Z","timestamp":1038700800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/journals\/pages\/open_access\/funder_policies\/chorus\/standard_publication_model"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2002,12,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>Secondary hyperparathyroidism (2\u00b0 HPT), a common disorder in chronic renal failure (CRF) patients, is characterized by hypersecretion of parathyroid hormone (PTH), parathyroid hyperplasia, and decreased expression of the calcium-sensing receptor (CaR). Dietary phosphate loading promotes 2\u00b0 HPT, and phosphate restriction prevents and arrests 2\u00b0 HPT in CRF. This study examined the ability of phosphate restriction to restore parathyroid CaR expression and function. Uremic rats fed a 1.2% P diet for 2 weeks developed 2\u00b0 HPT with down-regulated CaR expression. Continuation on the 1.2% P diet for 2 more weeks worsened the 2\u00b0 HPT and further decreased CaR, but switching the rats to a 0.2% P diet for 2 weeks normalized PTH, arrested parathyroid hyperplasia, and restored CaR expression to normal. The calcium-PTH relationship was abnormal in uremic rats fed a high phosphate (HP) diet with a right-shifted calcium set point but was corrected by 2 weeks of phosphate restriction. A time course revealed that following the switch to a low phosphate diet, PTH levels were normalized by day 1, and growth was arrested by day 2, but CaR expression was restored between days 7 and 14. We conclude that although phosphate restriction restores CaR expression and function in parathyroid glands of uremic rats, it is a late event and not involved in the arrest of 2\u00b0 HPT.<\/jats:p>","DOI":"10.1359\/jbmr.2002.17.12.2206","type":"journal-article","created":{"date-parts":[[2006,4,26]],"date-time":"2006-04-26T21:00:53Z","timestamp":1146085253000},"page":"2206-2213","source":"Crossref","is-referenced-by-count":60,"title":["Reversal of Secondary Hyperparathyroidism by Phosphate Restriction Restores Parathyroid Calcium-Sensing Receptor Expression and Function"],"prefix":"10.1093","volume":"17","author":[{"given":"Cynthia S.","family":"Ritter","sequence":"first","affiliation":[{"name":"Renal Division, Washington University School of Medicine, St. Louis, Missouri, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Daniel R.","family":"Martin","sequence":"additional","affiliation":[{"name":"Renal Division, Washington University School of Medicine, St. Louis, Missouri, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yan","family":"Lu","sequence":"additional","affiliation":[{"name":"Renal Division, Washington University School of Medicine, St. Louis, Missouri, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Eduardo","family":"Slatopolsky","sequence":"additional","affiliation":[{"name":"Renal Division, Washington University School of Medicine, St. Louis, Missouri, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Alex J.","family":"Brown","sequence":"additional","affiliation":[{"name":"Renal Division, Washington University School of Medicine, St. Louis, Missouri, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"286","published-online":{"date-parts":[[2009,12,2]]},"reference":[{"key":"2024013019054724000_bib1","doi-asserted-by":"crossref","first-page":"S14","DOI":"10.1046\/j.1523-1755.1999.07304.x","article-title":"Pathogenesis of secondary hyperparathyroidism","volume":"73","author":"Slatopolsky","year":"1999","journal-title":"Kidney Int"},{"key":"2024013019054724000_bib2","doi-asserted-by":"crossref","first-page":"626","DOI":"10.1007\/s004670000355","article-title":"Molecular mechanisms of secondary hyperparathyroidism","volume":"14","author":"Silver","year":"2000","journal-title":"Pediatr Nephrol"},{"key":"2024013019054724000_bib3","doi-asserted-by":"crossref","first-page":"370","DOI":"10.1097\/00000441-199906000-00004","article-title":"The role of phosphorus in the development of secondary hyperparathyroidism and parathyroid cell proliferation in chronic renal failure","volume":"317","author":"Slatopolsky","year":"1999","journal-title":"Am J Med Sci"},{"key":"2024013019054724000_bib4","doi-asserted-by":"crossref","first-page":"596","DOI":"10.1016\/S0272-6386(96)90473-4","article-title":"Phosphorus accelerates the development of parathyroid hyperplasia and secondary hyperparathyroidism in rats with renal failure","volume":"28","author":"Denda","year":"1996","journal-title":"Am J Kidney Dis"},{"key":"2024013019054724000_bib5","first-page":"F432","article-title":"Phosphorus restriction reverses hyperparathyroidism in uremia independent of changes in calcium and calcitriol","volume":"259","author":"Lopez-Hilker","year":"1990","journal-title":"Am J Physiol"},{"key":"2024013019054724000_bib6","doi-asserted-by":"crossref","first-page":"1786","DOI":"10.1172\/JCI118224","article-title":"Parathyroid cell proliferation in normal and chronic renal failure rats. The effects of calcium, phosphate, and vitamin D","volume":"96","author":"Naveh-Many","year":"1995","journal-title":"J Clin Invest"},{"key":"2024013019054724000_bib7","doi-asserted-by":"crossref","first-page":"4558","DOI":"10.1210\/endo.137.11.8895317","article-title":"Parathyroid cell proliferation in the rat: Effect of age and of phosphate administration and recovery","volume":"137","author":"Wang","year":"1996","journal-title":"Endocrinology"},{"key":"2024013019054724000_bib8","first-page":"1598","article-title":"Reduced immunostaining for the extracellular Ca2+-sensing receptor in primary and secondary hyperparathyroidism","volume":"81","author":"Kifor","year":"1996","journal-title":"J Clin Endocrinol Metab"},{"key":"2024013019054724000_bib9","doi-asserted-by":"crossref","first-page":"328","DOI":"10.1038\/ki.1997.41","article-title":"Depressed expression of calcium receptor in parathyroid gland tissue of patients with hyperparathyroidism","volume":"51","author":"Gogusev","year":"1997","journal-title":"Kidney Int"},{"key":"2024013019054724000_bib10","first-page":"3481","article-title":"Tumor-specific decreased expression of calcium sensing receptor messenger ribonucleic acid in sporadic primary hyperparathyroidism","volume":"82","author":"Farnebo","year":"1997","journal-title":"J Clin Endocrinol Metab"},{"key":"2024013019054724000_bib11","doi-asserted-by":"crossref","first-page":"339","DOI":"10.1046\/j.1365-2265.2000.00933.x","article-title":"Calcium-sensing receptor expression and signaling in human parathyroid adenomas and primary hyperplasia","volume":"52","author":"Corbetta","year":"2000","journal-title":"Clin Endocrinol"},{"key":"2024013019054724000_bib12","doi-asserted-by":"crossref","first-page":"1284","DOI":"10.1046\/j.1523-1755.1999.00386.x","article-title":"Decreased calcium-sensing receptor expression in hyperplastic parathyroid glands of uremic rats: Role of dietary phosphate","volume":"55","author":"Brown","year":"1999","journal-title":"Kidney Int"},{"key":"2024013019054724000_bib13","doi-asserted-by":"crossref","first-page":"1980","DOI":"10.1111\/j.1523-1755.2000.00370.x","article-title":"Association of decreased calcium-sensing receptor expression with proliferation of parathyroid cells in secondary hyperparathyroidism","volume":"58","author":"Yano","year":"2000","journal-title":"Kidney Int"},{"key":"2024013019054724000_bib14","doi-asserted-by":"crossref","first-page":"1737","DOI":"10.1046\/j.1523-1755.2001.00027.x","article-title":"Parathyroid hyperplasia in uremic rats precedes down-regulation of the calcium receptor","volume":"60","author":"Ritter","year":"2001","journal-title":"Kidney Int"},{"key":"2024013019054724000_bib15","doi-asserted-by":"crossref","first-page":"1573","DOI":"10.1056\/NEJM198706183162504","article-title":"Reduced binding of [3H]1,25-dihydroxyvitamin D3 in the parathyroid glands of patients with renal failure","volume":"316","author":"Korkor","year":"1987","journal-title":"N Engl J Med"},{"key":"2024013019054724000_bib16","doi-asserted-by":"crossref","first-page":"350","DOI":"10.1038\/ki.1987.216","article-title":"Diminished parathyroid 1,25(OH)2D3 receptors in experimental uremia","volume":"32","author":"Merke","year":"1987","journal-title":"Kidney Int"},{"key":"2024013019054724000_bib17","doi-asserted-by":"crossref","first-page":"19","DOI":"10.1038\/ki.1989.3","article-title":"1,25-(OH)2D receptors are decreased in parathyroid glands from chronically uremic dogs","volume":"35","author":"Brown","year":"1989","journal-title":"Kidney Int"},{"key":"2024013019054724000_bib18","doi-asserted-by":"crossref","first-page":"961","DOI":"10.1210\/jcem-52-5-961","article-title":"Four-parameter model of the sigmoidal relationship between parathyroid hormone release and extracellular calcium concentration in normal and abnormal parathyroid tissue","volume":"52","author":"Brown","year":"1983","journal-title":"J Clin Endocrinol Metab"},{"key":"2024013019054724000_bib19","doi-asserted-by":"crossref","first-page":"23605","DOI":"10.1074\/jbc.273.36.23605","article-title":"Dimerization of the extracellular calcium-sensing receptor (CaR) on the cell surface of CaR-transfected HEK293 cells","volume":"273","author":"Bai","year":"1998","journal-title":"J Biol Chem"},{"key":"2024013019054724000_bib20","doi-asserted-by":"crossref","first-page":"2834","DOI":"10.1073\/pnas.96.6.2834","article-title":"Intermolecular interactions between dimeric calcium-sensing receptor monomers are important for its normal function","volume":"96","author":"Bai","year":"1999","journal-title":"Proc Natl Acad Sci USA"},{"key":"2024013019054724000_bib21","doi-asserted-by":"crossref","first-page":"5316","DOI":"10.1074\/jbc.M005958200","article-title":"The extracellular calcium-sensing receptor dimerizes through multiple types of intermolecular interactions","volume":"276","author":"Zhang","year":"2001","journal-title":"J Biol Chem"},{"key":"2024013019054724000_bib22","doi-asserted-by":"crossref","first-page":"436","DOI":"10.1172\/JCI109145","article-title":"Responsiveness of neoplastic and hyperplastic tissue to calcium in vitro","volume":"62","author":"Habener","year":"1978","journal-title":"J Clin Invest"},{"key":"2024013019054724000_bib23","doi-asserted-by":"crossref","first-page":"923","DOI":"10.1016\/0002-9343(79)90446-7","article-title":"Calcium-regulated parathyroid hormone release in primary hyperparathyroidism: Studies in vitro with dispersed cells","volume":"66","author":"Brown","year":"1979","journal-title":"Am J Med"},{"key":"2024013019054724000_bib24","doi-asserted-by":"crossref","first-page":"565","DOI":"10.1016\/0002-9343(81)90207-2","article-title":"Abnormal calcium-related PTH release in normal tissue from patients with adenoma","volume":"71","author":"Brown","year":"1981","journal-title":"Am J Med"},{"key":"2024013019054724000_bib25","doi-asserted-by":"crossref","first-page":"172","DOI":"10.1210\/jcem-54-1-172","article-title":"Abnormal regulation of parathyroid hormone release by calcium in secondary hyperparathyroidism due to chronic renal failure","volume":"54","author":"Brown","year":"1982","journal-title":"J Clin Endocrinol Metab"},{"key":"2024013019054724000_bib26","first-page":"408","article-title":"Regulation of parathyroid hormone release in primary and secondary hyperparathyroidism: Studies in vivo and in vitro","volume":"101","author":"Rudberg","year":"1982","journal-title":"Acta Endocrinologica"},{"key":"2024013019054724000_bib27","first-page":"715","article-title":"Calcium infusion suggests a \u201cset point\u201d abnormality of parathyroid gland function in familial benign hypercalcemia and more complex disturbances in primary hyperparathyroidism","volume":"76","author":"Khosla","year":"1993","journal-title":"J Clin Endocrinol Metab"},{"key":"2024013019054724000_bib28","doi-asserted-by":"crossref","first-page":"553","DOI":"10.1111\/j.1365-2362.1994.tb01106.x","article-title":"Inter-relationships betweeen the calcium set-points of Parfitt and Brown in primary hyperparathyroidism: A sequential citrate and calcium clamp study","volume":"24","author":"Schwarz","year":"1994","journal-title":"Eur J Clin Invest"},{"key":"2024013019054724000_bib29","doi-asserted-by":"crossref","first-page":"1349","DOI":"10.1172\/JCI114022","article-title":"Parathyroid hormone suppression by intravenous 1,25-dihydroxyvitamin D. A role for increased sensitivity to calcium","volume":"83","author":"Delmez","year":"1989","journal-title":"J Clin Invest"},{"key":"2024013019054724000_bib30","doi-asserted-by":"crossref","first-page":"771","DOI":"10.1038\/ki.1993.111","article-title":"Parathyroid gland function in chronic renal failure","volume":"43","author":"Felsenfeld","year":"1993","journal-title":"Kidney Int"},{"key":"2024013019054724000_bib31","doi-asserted-by":"crossref","first-page":"1371","DOI":"10.1681\/ASN.V651371","article-title":"Differences in the dynamics of parathyroid hormone secretion in hemodialysis patients with marked secondary hyperparathyroidism","volume":"6","author":"Felsenfeld","year":"1995","journal-title":"J Am Soc Nephrol"},{"key":"2024013019054724000_bib32","first-page":"1489","article-title":"Direct in vivo comparison of calcium-regulated parathyroid hormone secretion in normal volunteers and patients with secondary hyperparathyroidism","volume":"76","author":"Ramirez","year":"1993","journal-title":"J Clin Endocrinol Metab"},{"key":"2024013019054724000_bib33","doi-asserted-by":"crossref","first-page":"1713","DOI":"10.1038\/ki.1994.473","article-title":"Direct in vivo assessment of parathyroid hormone-calcium relationship curve in renal patients","volume":"46","author":"Messa","year":"1994","journal-title":"Kidney Int"},{"key":"2024013019054724000_bib34","doi-asserted-by":"crossref","first-page":"1663","DOI":"10.1038\/ki.1996.483","article-title":"Non-suppressible parathyroid hormone secretion is related to gland size in uremic secondary hyperparathyroidism","volume":"50","author":"Indridason","year":"1996","journal-title":"Kidney Int"},{"key":"2024013019054724000_bib35","doi-asserted-by":"crossref","first-page":"769","DOI":"10.1007\/BF02935679","article-title":"Parathyroid gland calcium receptor mRNA levels are unaffected by chronic renal insufficiency or low dietary calcium in rats","volume":"3","author":"Rogers","year":"1995","journal-title":"Endocrine"},{"key":"2024013019054724000_bib36","first-page":"E220","article-title":"Regulation of parathyroid hormone secretion by plasma calcium in aging rats","volume":"260","author":"Fox","year":"1991","journal-title":"Am J Physiol"},{"key":"2024013019054724000_bib37","doi-asserted-by":"crossref","first-page":"1332","DOI":"10.1046\/j.1523-1755.2002.00265.x","article-title":"Hyperplasia of the parathyroid glands without secondary hyperparathyroidism","volume":"61","author":"Takahashi","year":"2002","journal-title":"Kidney Int"},{"key":"2024013019054724000_bib38","first-page":"768A","article-title":"Parathyroid CaR and VDR mRNA in uremia and after reversal of uremia by an experimental kidney transplantation in rats","volume":"12","author":"Lewin","year":"2001","journal-title":"J Am Soc Nephrol"},{"key":"2024013019054724000_bib39","doi-asserted-by":"crossref","first-page":"1093","DOI":"10.1172\/JCI10523","article-title":"Primary hyperparathyroidism caused by parathyroid-targeted overexpression of cyclin D1 in transgenic mice","volume":"107","author":"Imanishi","year":"2001","journal-title":"J Clin Invest"},{"key":"2024013019054724000_bib40","doi-asserted-by":"crossref","first-page":"S31","DOI":"10.1046\/j.1523-1755.1999.07316.x","article-title":"Hyperphosphatemia in end-stage renal disease patients: Pathophysiological consequences","volume":"56","author":"Llach","year":"1999","journal-title":"Kidney Int"}],"container-title":["Journal of Bone and Mineral Research"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1359%2Fjbmr.2002.17.12.2206","content-type":"unspecified","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/academic.oup.com\/jbmr\/article-pdf\/17\/12\/2206\/56469459\/5650171213.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/jbmr\/article-pdf\/17\/12\/2206\/56469459\/5650171213.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,3,13]],"date-time":"2024-03-13T15:04:18Z","timestamp":1710342258000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/jbmr\/article\/17\/12\/2206-2213\/7592299"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2002,12,1]]},"references-count":40,"journal-issue":{"issue":"12","published-online":{"date-parts":[[2009,12,2]]},"published-print":{"date-parts":[[2002,12,1]]}},"URL":"https:\/\/doi.org\/10.1359\/jbmr.2002.17.12.2206","relation":{},"ISSN":["0884-0431","1523-4681"],"issn-type":[{"value":"0884-0431","type":"print"},{"value":"1523-4681","type":"electronic"}],"subject":[],"published-other":{"date-parts":[[2002,12,1]]},"published":{"date-parts":[[2002,12,1]]}}}