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J Clin Endocrinol Metab. 2016;101(6):2594-601.

A Possible Link Between Parathyroid Hormone Secretion and Local Regulation of GABA in Human Parathyroid Adenomas.

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제1저자 홍아람 · 교신저자 김상완

PMID 27070188 DOI 10.1210/jc.2015-4329 IF 5.4 내분비대사내과
소속 (1)
  1. 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.

Abstract

CONTEXT 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.

OBJECTIVE 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.

RESULTS 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).

CONCLUSIONS 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.

그 밖의 정보
출판 형태
Journal Article
저널
The Journal of clinical endocrinology and metabolism · eISSN 1945-7197
전자 출판
2016-04-12
MeSH
25-Hydroxyvitamin D3 1-alpha-Hydroxylase / metabolism · Adenoma / complications / metabolism / surgery · Adult · Aged · Female · Fibroblast Growth Factors / metabolism · Glucuronidase / metabolism · Glutamate Decarboxylase / metabolism · Humans · Hyperparathyroidism, Primary / etiology / metabolism / surgery · Klotho Proteins · Male · Middle Aged · Parathyroid Hormone / metabolism · Parathyroid Neoplasms / complications / metabolism / surgery · Parathyroidectomy · Receptors, Calcitriol / metabolism · Receptors, Calcium-Sensing / metabolism · Receptors, GABA-B / metabolism · Vitamin D3 24-Hydroxylase / metabolism · gamma-Aminobutyric Acid / metabolism
Substances
Parathyroid Hormone · Receptors, Calcitriol · Receptors, Calcium-Sensing · Receptors, GABA-B · gamma-Aminobutyric Acid · Fibroblast Growth Factors · Vitamin D3 24-Hydroxylase · 25-Hydroxyvitamin D3 1-alpha-Hydroxylase · Glucuronidase · Klotho Proteins · Glutamate Decarboxylase