Adenomatous human parathyroid cells exhibit impaired sensitivity tol-amino acids

Mun, H.-C., Brennan, Sarah C. ORCID: https://orcid.org/0000-0002-8719-4367, Delbridge, L., Wilkinson, M., Brown, E. M. and Conigrave, A. D. 2009. Adenomatous human parathyroid cells exhibit impaired sensitivity tol-amino acids. Journal of Clinical Endocrinology & Metabolism 94 (9) , pp. 3567-3574. 10.1210/jc.2008-2714

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Abstract

Context: Primary hyperparathyroidism, which occurs most commonly in patients with adenomatous disease of a single parathyroid gland, arises as a result of impaired extracellular Ca2+ (Ca2+o)-dependent feedback on PTH secretion, a process mediated by the calcium-sensing receptor (CaR). Objective: Because the Ca2+o sensitivity of the CaR is positively modulated by l-amino acids, we decided to investigate whether the impaired feedback of PTH secretion in adenomatous parathyroid cells might arise from decreased sensitivity to l-amino acids. Design: Samples of normal and adenomatous human parathyroid cells were prepared by collagenase treatment and then exposed in vitro to various concentrations of Ca2+o or the CaR-active amino acid, l-phenylalanine (l-Phe). Setting and Patients: Excess normal parathyroid tissue was obtained from parathyroid autotransplants at the time of thyroid surgery. Samples of adenomatous tissue were obtained from histologically confirmed parathyroid adenomas. Main Outcome Measures: The primary measure was sensitivity of Ca2+o-dependent PTH secretion to the amino acid l-Phe. The secondary measure was sensitivity of Ca2+o-dependent intracellular Ca2+ mobilization to l-Phe. Results: Parathyroid adenomas exhibited reduced sensitivity to the CaR-active amino acid l-Phe, which affected both Ca2+o-dependent PTH secretion and Ca2+o-dependent intracellular Ca2+ mobilization as a measure of CaR-dependent signaling in parathyroid cells. Conclusions: Impaired l-amino acid sensing by calcium-sensing receptors in adenomatous parathyroid cells contributes to the loss of feedback control of PTH secretion in primary hyperparathyroidism. The CaR’s amino acid binding site may be exploited as a target in the medical treatment of primary and perhaps other forms of hyperparathyroidism. Impaired l-amino acid sensing by calcium-sensing receptors in adenomatous parathyroid cells contributes to the loss of feedback control of PTH secretion in primary hyperparathyroidism.

Item Type:	Article
Date Type:	Publication
Status:	Published
Schools:	Biosciences
Publisher:	The Endocrine Society
ISSN:	0021-972X
Last Modified:	27 Oct 2022 09:26
URI:	https://orca.cardiff.ac.uk/id/eprint/65841

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