title: A Possible Link Between Parathyroid Hormone Secretion and Local Regulation of GABA in Human Parathyroid Adenomas.
abstract: γ-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.
  
  
  
  The objective of the study was to examine a possible link between GABABR1 and PTH secretion in human parathyroid adenoma Design and Methods: 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 α-klotho in parathyroid tissues from patients with parathyroid adenomas using immunohistochemistry.
  
  
  
  Expressions of CaSR, GABABR1, and VDR were significantly lower in PHPT patients than in control subjects (P < .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 < .001). There were no significant differences in CYP24A1, CYP27B1, fibroblast growth factor, and α-klotho expression between the two groups. Expression of GAD65/67 was significantly correlated with VDR, CYP24A1, CYP27B1, and α-klotho in PHPT (all P < .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 = -0.342, P = .005).
  
  
  
  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.
authors.affiliation: Departments of Internal Medicine (A.R.H., J.H.B., J.H.K., C.S.S., S.Y.K., S.W.K.) and Pathology (Y.A.K., H.S.M.), Seoul National University College of Medicine, and Departments of Pathology (Y.A.K.) and Internal Medicine (S.W.K.), Seoul Metropolitan Government Boramae Medical Center, Seoul 156-707, Republic of Korea.
authors.forename: A Ram
authors.initials: AR
authors.lastname: Hong
authors.affiliation: Departments of Internal Medicine (A.R.H., J.H.B., J.H.K., C.S.S., S.Y.K., S.W.K.) and Pathology (Y.A.K., H.S.M.), Seoul National University College of Medicine, and Departments of Pathology (Y.A.K.) and Internal Medicine (S.W.K.), Seoul Metropolitan Government Boramae Medical Center, Seoul 156-707, Republic of Korea.
authors.forename: Young A
authors.initials: YA
authors.lastname: Kim
authors.affiliation: Departments of Internal Medicine (A.R.H., J.H.B., J.H.K., C.S.S., S.Y.K., S.W.K.) and Pathology (Y.A.K., H.S.M.), Seoul National University College of Medicine, and Departments of Pathology (Y.A.K.) and Internal Medicine (S.W.K.), Seoul Metropolitan Government Boramae Medical Center, Seoul 156-707, Republic of Korea.
authors.forename: Jae Hyun
authors.initials: JH
authors.lastname: Bae
authors.affiliation: Departments of Internal Medicine (A.R.H., J.H.B., J.H.K., C.S.S., S.Y.K., S.W.K.) and Pathology (Y.A.K., H.S.M.), Seoul National University College of Medicine, and Departments of Pathology (Y.A.K.) and Internal Medicine (S.W.K.), Seoul Metropolitan Government Boramae Medical Center, Seoul 156-707, Republic of Korea.
authors.forename: Hye Sook
authors.initials: HS
authors.lastname: Min
authors.affiliation: Departments of Internal Medicine (A.R.H., J.H.B., J.H.K., C.S.S., S.Y.K., S.W.K.) and Pathology (Y.A.K., H.S.M.), Seoul National University College of Medicine, and Departments of Pathology (Y.A.K.) and Internal Medicine (S.W.K.), Seoul Metropolitan Government Boramae Medical Center, Seoul 156-707, Republic of Korea.
authors.forename: Jung Hee
authors.initials: JH
authors.lastname: Kim
authors.affiliation: Departments of Internal Medicine (A.R.H., J.H.B., J.H.K., C.S.S., S.Y.K., S.W.K.) and Pathology (Y.A.K., H.S.M.), Seoul National University College of Medicine, and Departments of Pathology (Y.A.K.) and Internal Medicine (S.W.K.), Seoul Metropolitan Government Boramae Medical Center, Seoul 156-707, Republic of Korea.
authors.forename: Chan Soo
authors.initials: CS
authors.lastname: Shin
authors.affiliation: Departments of Internal Medicine (A.R.H., J.H.B., J.H.K., C.S.S., S.Y.K., S.W.K.) and Pathology (Y.A.K., H.S.M.), Seoul National University College of Medicine, and Departments of Pathology (Y.A.K.) and Internal Medicine (S.W.K.), Seoul Metropolitan Government Boramae Medical Center, Seoul 156-707, Republic of Korea.
authors.forename: Seong Yeon
authors.initials: SY
authors.lastname: Kim
authors.affiliation: Departments of Internal Medicine (A.R.H., J.H.B., J.H.K., C.S.S., S.Y.K., S.W.K.) and Pathology (Y.A.K., H.S.M.), Seoul National University College of Medicine, and Departments of Pathology (Y.A.K.) and Internal Medicine (S.W.K.), Seoul Metropolitan Government Boramae Medical Center, Seoul 156-707, Republic of Korea.
authors.forename: Sang Wan
authors.initials: SW
authors.lastname: Kim
mesh_terms: D015090:25-Hydroxyvitamin D3 1-alpha-Hydroxylase / Q000378:metabolism; D000236:Adenoma / Q000150:complications / Q000378:metabolism* / Q000601:surgery; D000328:Adult; D000368:Aged; D005260:Female; D005346:Fibroblast Growth Factors / Q000378:metabolism; D005966:Glucuronidase / Q000378:metabolism; D005968:Glutamate Decarboxylase / Q000378:metabolism; D006801:Humans; D049950:Hyperparathyroidism, Primary / Q000209:etiology / Q000378:metabolism* / Q000601:surgery; D000090265:Klotho Proteins; D008297:Male; D008875:Middle Aged; D010281:Parathyroid Hormone / Q000378:metabolism*; D010282:Parathyroid Neoplasms / Q000150:complications / Q000378:metabolism* / Q000601:surgery; D016105:Parathyroidectomy; D018167:Receptors, Calcitriol / Q000378:metabolism; D044169:Receptors, Calcium-Sensing / Q000378:metabolism; D018080:Receptors, GABA-B / Q000378:metabolism*; D065668:Vitamin D3 24-Hydroxylase / Q000378:metabolism; D005680:gamma-Aminobutyric Acid / Q000378:metabolism*
chemical_list: D010281:Parathyroid Hormone; D018167:Receptors, Calcitriol; D044169:Receptors, Calcium-Sensing; D018080:Receptors, GABA-B; D005680:gamma-Aminobutyric Acid; D005346:Fibroblast Growth Factors; D065668:Vitamin D3 24-Hydroxylase; D015090:25-Hydroxyvitamin D3 1-alpha-Hydroxylase; D005966:Glucuronidase; D000090265:Klotho Proteins; D005968:Glutamate Decarboxylase