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.