{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,22]],"date-time":"2026-09-22T04:41:07Z","timestamp":1790052067224,"version":"4.0.1"},"reference-count":39,"publisher":"The Endocrine Society","issue":"11","license":[{"start":{"date-parts":[[2023,9,11]],"date-time":"2023-09-11T00:00:00Z","timestamp":1694390400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"funder":[{"DOI":"10.13039\/100000002","name":"NIH","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000062","name":"NIDDK","doi-asserted-by":"publisher","award":["R01DK066411"],"award-info":[{"award-number":["R01DK066411"]}],"id":[{"id":"10.13039\/100000062","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2023,9,23]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Primary hyperparathyroidism (PHPT) is a common endocrinopathy for which several pathogenic mechanisms, including cyclin D1 overexpression, have been identified. Vitamin D nutritional status may influence parathyroid tumorigenesis, but evidence remains circumstantial. To assess the potential influence of vitamin D insufficiency\/deficiency on initiation or progression of parathyroid tumorigenesis, we superimposed vitamin D insufficiency or deficiency on parathyroid tumor\u2013prone parathyroid hormone\u2013cyclin D1 transgenic mice. Mice were placed on diets containing either 2.75\u2005IU\/g, 0.25\u2005IU\/g, or 0.05\u2005IU\/g cholecalciferol, either prior to expected onset of PHPT or after onset of biochemical PHPT. When introduced early, superimposed vitamin D insufficiency\/deficiency had no effect on serum calcium or on parathyroid gland growth. However, when introduced after the onset of biochemical PHPT, vitamin D deficiency led to larger parathyroid glands without differences in serum biochemical parameters. Our results suggest that low vitamin D status enhances proliferation of parathyroid cells whose growth is already being tumorigenically driven, in contrast to its apparent lack of direct proliferation-initiating action on normally growing parathyroid cells in this model. These results are consistent with the hypothesis that suboptimal vitamin D status may not increase incidence of de novo parathyroid tumorigenesis but may accelerate growth of a preexisting parathyroid tumor.<\/jats:p>","DOI":"10.1210\/endocr\/bqad137","type":"journal-article","created":{"date-parts":[[2023,9,11]],"date-time":"2023-09-11T10:18:09Z","timestamp":1694427489000},"source":"Crossref","is-referenced-by-count":6,"title":["Influence of Vitamin D Deficiency on Cyclin D1-Induced Parathyroid Tumorigenesis"],"prefix":"10.1210","volume":"164","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-6437-1693","authenticated-orcid":false,"given":"Jessica","family":"Costa-Guda","sequence":"first","affiliation":[{"name":"Center for Regenerative Medicine and Skeletal Development, University of Connecticut School of Dental Medicine , Farmington, CT 06030-3101 , USA"},{"name":"Center for Molecular Oncology, University of Connecticut School of Medicine , Farmington, CT 06030-3101 , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kristin","family":"Corrado","sequence":"additional","affiliation":[{"name":"Center for Molecular Oncology, University of Connecticut School of Medicine , Farmington, CT 06030-3101 , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Justin","family":"Bellizzi","sequence":"additional","affiliation":[{"name":"Center for Molecular Oncology, University of Connecticut School of Medicine , Farmington, CT 06030-3101 , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elizabeth","family":"Saria","sequence":"additional","affiliation":[{"name":"Center for Molecular Oncology, University of Connecticut School of Medicine , Farmington, CT 06030-3101 , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kirsten","family":"Saucier","sequence":"additional","affiliation":[{"name":"Center for Molecular Oncology, University of Connecticut School of Medicine , Farmington, CT 06030-3101 , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Miriam","family":"Guemes-Aragon","sequence":"additional","affiliation":[{"name":"Section of Oral and Maxillofacial Radiology, UCLA School of Dentistry , Los Angeles, CA 90095 , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Guntas","family":"Kakar","sequence":"additional","affiliation":[{"name":"Section of Oral and Maxillofacial Radiology, UCLA School of Dentistry , Los Angeles, CA 90095 , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Madison","family":"Rose","sequence":"additional","affiliation":[{"name":"Center for Molecular Oncology, University of Connecticut School of Medicine , Farmington, CT 06030-3101 , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Melanie","family":"Pascal","sequence":"additional","affiliation":[{"name":"Center for Molecular Oncology, University of Connecticut School of Medicine , Farmington, CT 06030-3101 , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cynthia","family":"Alander","sequence":"additional","affiliation":[{"name":"Center for Molecular Oncology, University of Connecticut School of Medicine , Farmington, CT 06030-3101 , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sanjay M","family":"Mallya","sequence":"additional","affiliation":[{"name":"Section of Oral and Maxillofacial Radiology, UCLA School of Dentistry , Los Angeles, CA 90095 , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8821-8527","authenticated-orcid":false,"given":"Andrew","family":"Arnold","sequence":"additional","affiliation":[{"name":"Center for Molecular Oncology, University of Connecticut School of Medicine , Farmington, CT 06030-3101 , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"80","published-online":{"date-parts":[[2023,9,11]]},"reference":[{"issue":"11","key":"2023092317114048600_bqad137-B1","doi-asserted-by":"crossref","first-page":"2330","DOI":"10.1002\/jbmr.4679","article-title":"Classical and nonclassical manifestations of primary hyperparathyroidism","volume":"37","author":"El-Hajj Fuleihan","year":"2022","journal-title":"J Bone Miner Res"},{"issue":"4","key":"2023092317114048600_bqad137-B2","first-page":"701","article-title":"Vitamin D in normal and pathological parathyroid glands: new prospects for treating hyperparathyroidism (review)","volume":"15","author":"Buchwald","year":"2005","journal-title":"Int J Mol Med"},{"issue":"Suppl 2","key":"2023092317114048600_bqad137-B3","first-page":"N75","article-title":"Role of vitamin D and calcium nutrition in disease expression and parathyroid tumor growth in primary hyperparathyroidism: a global perspective","volume":"17","author":"Rao","year":"2002","journal-title":"J Bone Miner Res"},{"issue":"Suppl 2","key":"2023092317114048600_bqad137-B4","doi-asserted-by":"crossref","first-page":"V100","DOI":"10.1359\/jbmr.07s202","article-title":"Vitamin D deficiency and primary hyperparathyroidism","volume":"22","author":"Silverberg","year":"2007","journal-title":"J Bone Miner Res"},{"key":"2023092317114048600_bqad137-B5","doi-asserted-by":"crossref","first-page":"105695","DOI":"10.1016\/j.jsbmb.2020.105695","article-title":"Effect of vitamin D nutrition on disease indices in patients with primary hyperparathyroidism","volume":"201","author":"Rao","year":"2020","journal-title":"J Steroid Biochem Mol Biol"},{"key":"2023092317114048600_bqad137-B6","doi-asserted-by":"crossref","first-page":"1009516","DOI":"10.3389\/fendo.2023.1009516","article-title":"Large parathyroid adenomas: potential mechanisms to reconcile adenoma size and disease phenotype","volume":"14","author":"Bhan","year":"2023","journal-title":"Front Endocrinol (Lausanne)"},{"issue":"9","key":"2023092317114048600_bqad137-B7","doi-asserted-by":"crossref","first-page":"3443","DOI":"10.1210\/jc.2015-2022","article-title":"Vitamin D in primary hyperparathyroidism: effects on clinical, biochemical, and densitometric presentation","volume":"100","author":"Walker","year":"2015","journal-title":"J Clin Endocrinol Metab"},{"issue":"9","key":"2023092317114048600_bqad137-B8","doi-asserted-by":"crossref","first-page":"e842","DOI":"10.1210\/clinem\/dgad103","article-title":"Morbidity associated with primary hyperparathyroidism\u2014A population-based study with a sub-analysis on vitamin D","volume":"108","author":"Soto-Pedre","year":"2023","journal-title":"J Clin Endocrinol Metab"},{"issue":"4","key":"2023092317114048600_bqad137-B9","doi-asserted-by":"crossref","first-page":"871","DOI":"10.1016\/j.ecl.2017.07.003","article-title":"Dietary vitamin D intake for the elderly population: update on the recommended dietary allowance for vitamin D","volume":"46","author":"Smith","year":"2017","journal-title":"Endocrinol Metab Clin North Am"},{"issue":"11","key":"2023092317114048600_bqad137-B10","doi-asserted-by":"crossref","first-page":"2391","DOI":"10.1002\/jbmr.4682","article-title":"Management of primary hyperparathyroidism","volume":"37","author":"Bilezikian","year":"2022","journal-title":"J Bone Miner Res"},{"issue":"2","key":"2023092317114048600_bqad137-B11","first-page":"123","article-title":"Effect of gender and geographic location on the expression of primary hyperparathyroidism","volume":"36","author":"De Lucia","year":"2013","journal-title":"J Endocrinol Invest"},{"issue":"2","key":"2023092317114048600_bqad137-B12","doi-asserted-by":"crossref","first-page":"162","DOI":"10.4248\/BR201302005","article-title":"Primary hyperparathyroidism: A tale of two cities revisited\u2014New York and Shanghai","volume":"1","author":"Liu","year":"2013","journal-title":"Bone Res"},{"issue":"1","key":"2023092317114048600_bqad137-B13","doi-asserted-by":"crossref","first-page":"3","DOI":"10.1007\/s12020-016-1169-1","article-title":"Vitamin D and primary hyperparathyroidism: more insights into a complex relationship","volume":"55","author":"Walker","year":"2017","journal-title":"Endocrine"},{"issue":"17","key":"2023092317114048600_bqad137-B14","doi-asserted-by":"crossref","first-page":"8097","DOI":"10.1073\/pnas.89.17.8097","article-title":"Sequences in the human parathyroid hormone gene that bind the 1,25-dihydroxyvitamin D3 receptor and mediate transcriptional repression in response to 1,25-dihydroxyvitamin D3","volume":"89","author":"Demay","year":"1992","journal-title":"Proc Natl Acad Sci U S A"},{"key":"2023092317114048600_bqad137-B15","doi-asserted-by":"crossref","first-page":"S2","DOI":"10.1046\/j.1523-1755.1999.07310.x","article-title":"Regulation of the parathyroid hormone gene by vitamin D, calcium and phosphate","volume":"73","author":"Silver","year":"1999","journal-title":"Kidney Int Suppl"},{"issue":"4","key":"2023092317114048600_bqad137-B16","doi-asserted-by":"crossref","first-page":"213","DOI":"10.1007\/BF02555137","article-title":"1,25(OH)2D3 Inhibits hormone secretion and proliferation but not functional dedifferentiation of cultured bovine parathyroid cells","volume":"43","author":"Nygren","year":"1988","journal-title":"Calcif Tissue Int"},{"issue":"5","key":"2023092317114048600_bqad137-B17","doi-asserted-by":"crossref","first-page":"2114","DOI":"10.1210\/endo-117-5-2114","article-title":"1,25-Dihydroxyvitamin D3 suppresses parathyroid hormone secretion from bovine parathyroid cells in tissue culture","volume":"117","author":"Cantley","year":"1985","journal-title":"Endocrinology"},{"issue":"4","key":"2023092317114048600_bqad137-B18","doi-asserted-by":"crossref","first-page":"1049","DOI":"10.1038\/ki.1989.89","article-title":"1,25(OH)2 Vitamin D3 inhibits parathyroid cell proliferation in experimental uremia","volume":"35","author":"Szabo","year":"1989","journal-title":"Kidney Int"},{"issue":"1","key":"2023092317114048600_bqad137-B19","doi-asserted-by":"crossref","first-page":"365","DOI":"10.1152\/physrev.00014.2015","article-title":"Vitamin D: metabolism, molecular mechanism of action, and pleiotropic effects","volume":"96","author":"Christakos","year":"2016","journal-title":"Physiol Rev"},{"issue":"6","key":"2023092317114048600_bqad137-B20","doi-asserted-by":"crossref","first-page":"561","DOI":"10.1016\/S0002-9343(99)00294-6","article-title":"The effects of vitamin D insufficiency in patients with primary hyperparathyroidism","volume":"107","author":"Silverberg","year":"1999","journal-title":"Am J Med"},{"issue":"1","key":"2023092317114048600_bqad137-B21","doi-asserted-by":"crossref","first-page":"17","DOI":"10.1111\/j.1365-2265.1992.tb02278.x","article-title":"The role of 1,25-dihydroxyvitamin D in the mechanism of acquired vitamin D deficiency","volume":"37","author":"Clements","year":"1992","journal-title":"Clin Endocrinol (Oxf)"},{"issue":"11","key":"2023092317114048600_bqad137-B22","doi-asserted-by":"crossref","first-page":"e10415","DOI":"10.1002\/jbm4.10415","article-title":"Low 25-hydroxyvitamin D in primary hyperparathyroidism: enhanced conversion into 1,25-hydroxyvitamin D may not be \u201ctrue\u201d deficiency","volume":"4","author":"Kabadi","year":"2020","journal-title":"JBMR Plus"},{"issue":"6","key":"2023092317114048600_bqad137-B23","doi-asserted-by":"crossref","first-page":"659","DOI":"10.1042\/cs0730659","article-title":"Metabolic inactivation of vitamin D is enhanced in primary hyperparathyroidism","volume":"73","author":"Clements","year":"1987","journal-title":"Clin Sci (Lond)"},{"issue":"5","key":"2023092317114048600_bqad137-B24","doi-asserted-by":"crossref","first-page":"859","DOI":"10.3945\/jn.111.149914","article-title":"Dietary cholecalciferol and calcium levels in a western-style defined rodent diet alter energy metabolism and inflammatory responses in mice","volume":"142","author":"Bastie","year":"2012","journal-title":"J Nutr"},{"issue":"9","key":"2023092317114048600_bqad137-B25","doi-asserted-by":"crossref","first-page":"1658","DOI":"10.1093\/jn\/138.9.1658","article-title":"Dietary calcium and cholecalciferol modulate cyclin D1 expression, apoptosis, and tumorigenesis in intestine of adenomatous polyposis coli1638N\/+ mice","volume":"138","author":"Yang","year":"2008","journal-title":"J Nutr"},{"issue":"6","key":"2023092317114048600_bqad137-B26","doi-asserted-by":"crossref","first-page":"2423","DOI":"10.1210\/en.2010-0089","article-title":"Vitamin D deficiency in mice impairs colonic antibacterial activity and predisposes to colitis","volume":"151","author":"Lagishetty","year":"2010","journal-title":"Endocrinology"},{"issue":"10","key":"2023092317114048600_bqad137-B27","doi-asserted-by":"crossref","first-page":"1617","DOI":"10.1158\/1940-6207.CAPR-11-0035","article-title":"Dietary vitamin D and vitamin D receptor level modulate epithelial cell proliferation and apoptosis in the prostate","volume":"4","author":"Kovalenko","year":"2011","journal-title":"Cancer Prev Res (Phila)"},{"issue":"9","key":"2023092317114048600_bqad137-B28","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"},{"issue":"10","key":"2023092317114048600_bqad137-B29","doi-asserted-by":"crossref","first-page":"2603","DOI":"10.1210\/me.2005-0116","article-title":"Abnormal parathyroid cell proliferation precedes biochemical abnormalities in a mouse model of primary hyperparathyroidism","volume":"19","author":"Mallya","year":"2005","journal-title":"Mol Endocrinol"},{"issue":"4","key":"2023092317114048600_bqad137-B30","doi-asserted-by":"crossref","first-page":"290","DOI":"10.3109\/07435800.2016.1141937","article-title":"Modeling vitamin D insufficiency and moderate deficiency in adult mice via dietary cholecalciferol restriction","volume":"41","author":"Mallya","year":"2016","journal-title":"Endocr Res"},{"issue":"11","key":"2023092317114048600_bqad137-B31","doi-asserted-by":"crossref","first-page":"1000","DOI":"10.1002\/hed.10165","article-title":"Correlation of biochemical parameters with single parathyroid adenoma weight and volume","volume":"24","author":"Bindlish","year":"2002","journal-title":"Head Neck"},{"issue":"4","key":"2023092317114048600_bqad137-B32","doi-asserted-by":"crossref","first-page":"330","DOI":"10.1016\/j.bjoms.2019.03.007","article-title":"Detectability and surgical outcomes in parathyroid surgery\u2014a single-centre experience","volume":"57","author":"Borumandi","year":"2019","journal-title":"Br J Oral Maxillofac Surg"},{"issue":"11","key":"2023092317114048600_bqad137-B33","doi-asserted-by":"crossref","first-page":"1957","DOI":"10.1097\/MLG.0b013e31813c14fc","article-title":"Correlation of intraoperative parathyroid hormone levels with parathyroid gland size","volume":"117","author":"Moretz","year":"2007","journal-title":"Laryngoscope"},{"issue":"10","key":"2023092317114048600_bqad137-B34","doi-asserted-by":"crossref","first-page":"882","DOI":"10.1111\/j.1445-2197.2006.03896.x","article-title":"Are biochemical values predictive of adenoma's Weight in primary hyperparathyroidism?","volume":"76","author":"Hamidi","year":"2006","journal-title":"ANZ J Surg"},{"issue":"2","key":"2023092317114048600_bqad137-B35","doi-asserted-by":"crossref","first-page":"501","DOI":"10.1007\/s00423-021-02406-3","article-title":"Giant parathyroid tumours in primary hyperparathyroidism: a systematic review","volume":"407","author":"Wong","year":"2022","journal-title":"Langenbecks Arch Surg"},{"issue":"6","key":"2023092317114048600_bqad137-B36","first-page":"1107","article-title":"The relation of serum calcium and immunoparathormone levels to parathyroid size and weight in primary hyperparathyroidism","volume":"98","author":"Rutledge","year":"1985","journal-title":"Surgery"},{"issue":"3","key":"2023092317114048600_bqad137-B37","doi-asserted-by":"crossref","first-page":"179","DOI":"10.1111\/j.1365-2273.2007.01447.x","article-title":"Primary hyperparathyroidism: do perioperative biochemical variables correlate with parathyroid adenoma weight or volume?","volume":"32","author":"Randhawa","year":"2007","journal-title":"Clin Otolaryngol"},{"issue":"5","key":"2023092317114048600_bqad137-B38","first-page":"840","article-title":"Can the volume of abnormal parathyroid tissue be predicted by preoperative biochemical measurement?","volume":"102","author":"Saxe","year":"1987","journal-title":"Surgery"},{"issue":"5","key":"2023092317114048600_bqad137-B39","doi-asserted-by":"crossref","first-page":"1032","DOI":"10.1210\/jcem-60-5-1032","article-title":"Parathyroid hormone secretion from dispersed human hyperparathyroid cells: increased secretion in cells from hyperplastic glands versus adenomas","volume":"60","author":"Cantley","year":"1985","journal-title":"J Clin Endocrinol Metab"}],"container-title":["Endocrinology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/academic.oup.com\/endo\/advance-article-pdf\/doi\/10.1210\/endocr\/bqad137\/51507359\/bqad137.pdf","content-type":"application\/pdf","content-version":"am","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/endo\/article-pdf\/164\/11\/bqad137\/51730711\/bqad137.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/endo\/article-pdf\/164\/11\/bqad137\/51730711\/bqad137.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,10,27]],"date-time":"2024-10-27T21:27:53Z","timestamp":1730064473000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/endo\/article\/doi\/10.1210\/endocr\/bqad137\/7267595"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,9,11]]},"references-count":39,"journal-issue":{"issue":"11","published-print":{"date-parts":[[2023,9,23]]}},"URL":"https:\/\/doi.org\/10.1210\/endocr\/bqad137","relation":{},"ISSN":["1945-7170"],"issn-type":[{"value":"1945-7170","type":"electronic"}],"subject":[],"published-other":{"date-parts":[[2023,11]]},"published":{"date-parts":[[2023,9,11]]},"article-number":"bqad137"}}