{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,28]],"date-time":"2026-03-28T08:16:18Z","timestamp":1774685778505,"version":"3.50.1"},"reference-count":28,"publisher":"The Endocrine Society","issue":"6","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2016,6,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:sec>\n                  <jats:title>Context:<\/jats:title>\n                  <jats:p>\u03b3-Aminobutyric acid-B receptor 1 (GABABR1) forms a heterodimeric complex with calcium-sensing receptor (CaSR) in human brain tissue. However, the expression and implication of GABABR1 in human parathyroid adenoma has not yet been examined.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Objective:<\/jats:title>\n                  <jats:p>The objective of the study was to examine a possible link between GABABR1 and PTH secretion in human parathyroid adenoma<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Design and Methods:<\/jats:title>\n                  <jats:p>Sixty-five patients who underwent parathyroidectomy for primary hyperparathyroidism (PHPT) and 29 control patients with normal parathyroid glands were retrospectively included. All patients diagnosed with PHPT had parathyroid adenomas. We evaluated the protein expression of GABABR1, glutamic acid decarboxylase 65\/67 (GAD65\/67), and various factors proposed as regulators of PTH secretion including CaSR, vitamin D receptor (VDR), CYP24A1, CYP27B1, fibroblast growth factor, and \u03b1-klotho in parathyroid tissues from patients with parathyroid adenomas using immunohistochemistry.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Results:<\/jats:title>\n                  <jats:p>Expressions of CaSR, GABABR1, and VDR were significantly lower in PHPT patients than in control subjects (P &amp;lt; .001 for CaSR and GABABR1; P = .006 for VDR). Protein expression of GAD65\/67, which indicates local production and regulation of GABAergic pathway, was significantly increased in PHPT (P &amp;lt; .001). There were no significant differences in CYP24A1, CYP27B1, fibroblast growth factor, and \u03b1-klotho expression between the two groups. Expression of GAD65\/67 was significantly correlated with VDR, CYP24A1, CYP27B1, and \u03b1-klotho in PHPT (all P &amp;lt; .01) but not in the control groups. CaSR expression was positively associated with serum phosphorus level (r = 0.274, P = .029) and GAD65\/67 was negatively correlated with serum PTH level (r = \u22120.342, P = .005).<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Conclusions:<\/jats:title>\n                  <jats:p>Local production and action of GABA may be regulated in human parathyroid adenomas. This suggests a possible link between PTH secretion and local regulation of GABA in parathyroid adenomas.<\/jats:p>\n               <\/jats:sec>","DOI":"10.1210\/jc.2015-4329","type":"journal-article","created":{"date-parts":[[2016,4,12]],"date-time":"2016-04-12T17:01:36Z","timestamp":1460480496000},"page":"2594-2601","source":"Crossref","is-referenced-by-count":10,"title":["A Possible Link Between Parathyroid Hormone Secretion and Local Regulation of GABA in Human Parathyroid Adenomas"],"prefix":"10.1210","volume":"101","author":[{"given":"A Ram","family":"Hong","sequence":"first","affiliation":[{"name":"Departments of Internal Medicine (A.R.H., J.H.B., J.H.K., C.S.S., S.Y.K., S.W.K.), Seoul 156-707, Republic of Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Young A","family":"Kim","sequence":"additional","affiliation":[{"name":"Seoul National University College of Medicine, and Departments of Pathology (Y.A.K.), Seoul 156-707, Republic of Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jae Hyun","family":"Bae","sequence":"additional","affiliation":[{"name":"Departments of Internal Medicine (A.R.H., J.H.B., J.H.K., C.S.S., S.Y.K., S.W.K.), Seoul 156-707, Republic of Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hye Sook","family":"Min","sequence":"additional","affiliation":[{"name":"Pathology (Y.A.K., H.S.M.), Seoul 156-707, Republic of Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jung Hee","family":"Kim","sequence":"additional","affiliation":[{"name":"Departments of Internal Medicine (A.R.H., J.H.B., J.H.K., C.S.S., S.Y.K., S.W.K.), Seoul 156-707, Republic of Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Chan Soo","family":"Shin","sequence":"additional","affiliation":[{"name":"Departments of Internal Medicine (A.R.H., J.H.B., J.H.K., C.S.S., S.Y.K., S.W.K.), Seoul 156-707, Republic of Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Seong Yeon","family":"Kim","sequence":"additional","affiliation":[{"name":"Departments of Internal Medicine (A.R.H., J.H.B., J.H.K., C.S.S., S.Y.K., S.W.K.), Seoul 156-707, Republic of Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sang Wan","family":"Kim","sequence":"additional","affiliation":[{"name":"Departments of Internal Medicine (A.R.H., J.H.B., J.H.K., C.S.S., S.Y.K., S.W.K.), Seoul 156-707, Republic of Korea"},{"name":"Internal Medicine (S.W.K.), Seoul Metropolitan Government Boramae Medical Center, Seoul 156-707, Republic of Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"80","reference":[{"key":"2020071614170457500_B1","doi-asserted-by":"crossref","first-page":"54","DOI":"10.1053\/hupa.2003.55","article-title":"Parathyroid neoplasms: clinical, histopathological, and tissue microarray-based molecular analysis","volume":"34","author":"Stojadinovic","year":"2003","journal-title":"Hum Pathol"},{"key":"2020071614170457500_B2","doi-asserted-by":"crossref","first-page":"494","DOI":"10.1006\/bbrc.2000.3696","article-title":"Identification of a novel fibroblast growth factor, FGF-23, preferentially expressed in the ventrolateral thalamic nucleus of the brain","volume":"277","author":"Yamashita","year":"2000","journal-title":"Biochem Biophys Res Commun"},{"key":"2020071614170457500_B3","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":"2020071614170457500_B4","first-page":"4003","article-title":"The parathyroid is a target organ for FGF23 in rats","volume":"117","author":"Ben-Dov","year":"2007","journal-title":"J Clin Invest"},{"key":"2020071614170457500_B5","doi-asserted-by":"crossref","first-page":"255","DOI":"10.1007\/s12020-013-9881-6","article-title":"Involvement of alpha-klotho, fibroblast growth factor-, vitamin-D- and calcium-sensing receptor in 53 patients with primary hyperparathyroidism","volume":"44","author":"Latus","year":"2013","journal-title":"Endocrine"},{"key":"2020071614170457500_B6","doi-asserted-by":"crossref","first-page":"4152","DOI":"10.1210\/jc.2008-0564","article-title":"Type I membrane klotho expression is decreased and inversely correlated to serum calcium in primary hyperparathyroidism","volume":"93","author":"Bjorklund","year":"2008","journal-title":"J Clin Endocrinol Metab"},{"key":"2020071614170457500_B7","doi-asserted-by":"crossref","first-page":"25030","DOI":"10.1074\/jbc.M700924200","article-title":"Complex formation with the type B \u03b3-aminobutyric acid receptor affects the expression and signal transduction of the extracellular calcium-sensing receptor. Studies with HEK-293 cells and neurons","volume":"282","author":"Chang","year":"2007","journal-title":"J Biol Chem"},{"key":"2020071614170457500_B8","doi-asserted-by":"crossref","first-page":"851","DOI":"10.1002\/acn3.118","article-title":"Calcium-sensing receptor (CaSR) as a novel target for ischemic neuroprotection","volume":"1","author":"Kim","year":"2014","journal-title":"Ann Clin Transl Neurol"},{"key":"2020071614170457500_B9","doi-asserted-by":"crossref","first-page":"4984","DOI":"10.1210\/en.2007-0653","article-title":"Type B \u03b3-aminobutyric acid receptors modulate the function of the extracellular Ca2+-sensing receptor and cell differentiation in murine growth plate chondrocytes","volume":"148","author":"Cheng","year":"2007","journal-title":"Endocrinology"},{"key":"2020071614170457500_B10","article-title":"Parathyroid GABABR1 is the molecular basis for the development of hyperparathyroidism due to CaSR deficiency","author":"Chang"},{"key":"2020071614170457500_B11","doi-asserted-by":"crossref","first-page":"461","DOI":"10.7326\/0003-4819-130-6-199903160-00002","article-title":"A more accurate method to estimate glomerular filtration rate from serum creatinine: a new prediction equation. Modification of Diet in Renal Disease Study Group","volume":"130","author":"Levey","year":"1999","journal-title":"Ann Intern Med"},{"key":"2020071614170457500_B12","doi-asserted-by":"crossref","first-page":"1","DOI":"10.4143\/crt.2006.38.1.1","article-title":"Tissue array methods for high-throughput clinicopathologic research","volume":"38","author":"Lee","year":"2006","journal-title":"Cancer Res Treat"},{"key":"2020071614170457500_B13","first-page":"4789","article-title":"Parathyroid expression of calcium-sensing receptor protein and in vivo parathyroid hormone-Ca(2+) set-point in patients with primary hyperparathyroidism","volume":"85","author":"Cetani","year":"2000","journal-title":"J Clin Endocrinol Metab"},{"key":"2020071614170457500_B14","doi-asserted-by":"crossref","first-page":"265","DOI":"10.1016\/j.lungcan.2012.04.010","article-title":"Characterization of vitamin D receptor (VDR) in lung adenocarcinoma","volume":"77","author":"Kim","year":"2012","journal-title":"Lung 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Rao","year":"2000","journal-title":"Clin Endocrinol (Oxf)"},{"key":"2020071614170457500_B18","first-page":"2000","article-title":"Reduced parathyroid vitamin D receptor messenger ribonucleic acid levels in primary and secondary hyperparathyroidism","volume":"85","author":"Carling","year":"2000","journal-title":"J Clin Endocrinol Metab"},{"key":"2020071614170457500_B19","doi-asserted-by":"crossref","first-page":"F1192","DOI":"10.1152\/ajprenal.00360.2009","article-title":"Deletion of the vitamin D receptor specifically in the parathyroid demonstrates a limited role for the receptor in parathyroid physiology","volume":"297","author":"Meir","year":"2009","journal-title":"Am J Physiol Renal Physiol"},{"key":"2020071614170457500_B20","doi-asserted-by":"crossref","first-page":"620","DOI":"10.1126\/science.185693","article-title":"High concentration of GABA and high glutamate decarboxylase activity in rat pancreatic islets and human insulinoma","volume":"194","author":"Okada","year":"1976","journal-title":"Science"},{"key":"2020071614170457500_B21","doi-asserted-by":"crossref","first-page":"1321","DOI":"10.1016\/S0024-3205(99)00067-3","article-title":"Distribution of GABA(B) receptor mRNAs in the rat brain and peripheral organs","volume":"64","author":"Castelli","year":"1999","journal-title":"Life Sci"},{"key":"2020071614170457500_B22","doi-asserted-by":"crossref","first-page":"397","DOI":"10.1113\/jphysiol.2004.066563","article-title":"GABAB receptor activation inhibits exocytosis in rat pancreatic \u03b2-cells by G-protein-dependent activation of calcineurin","volume":"559","author":"Braun","year":"2004","journal-title":"J Physiol"},{"key":"2020071614170457500_B23","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 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