| Adenomatous human parathyroid cells exhibit impaired sensitivity to L-amino acids. | |
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MedLine Citation:
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PMID: 19567535 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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CONTEXT: Primary hyperparathyroidism, which occurs most commonly in patients with adenomatous disease of a single parathyroid gland, arises as a result of impaired extracellular Ca(2+) (Ca(2+)(o))-dependent feedback on PTH secretion, a process mediated by the calcium-sensing receptor (CaR). OBJECTIVE: Because the Ca(2+)(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 Ca(2+)(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 Ca(2+)(o)-dependent PTH secretion to the amino acid L-Phe. The secondary measure was sensitivity of Ca(2+)(o)-dependent intracellular Ca(2+) mobilization to L-Phe. RESULTS: Parathyroid adenomas exhibited reduced sensitivity to the CaR-active amino acid L-Phe, which affected both Ca(2+)(o)-dependent PTH secretion and Ca(2+)(o)-dependent intracellular Ca(2+) 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. |
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Authors:
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H-C Mun; S C Brennan; L Delbridge; M Wilkinson; E M Brown; A D Conigrave |
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Publication Detail:
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Type: Journal Article Date: 2009-06-30 |
Journal Detail:
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Title: The Journal of clinical endocrinology and metabolism Volume: 94 ISSN: 1945-7197 ISO Abbreviation: J. Clin. Endocrinol. Metab. Publication Date: 2009 Sep |
Date Detail:
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Created Date: 2009-09-07 Completed Date: 2009-09-23 Revised Date: 2010-09-02 |
Medline Journal Info:
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Nlm Unique ID: 0375362 Medline TA: J Clin Endocrinol Metab Country: United States |
Other Details:
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Languages: eng Pagination: 3567-74 Citation Subset: AIM; IM |
Affiliation:
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School of Molecular and Microbial Biosciences, University of Sydney, New South Wales 2006, Australia. |
Export Citation:
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APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
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Adenoma
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secretion* Amino Acids / pharmacology* Calcium / metabolism Feedback, Physiological Humans Parathyroid Glands / metabolism Parathyroid Hormone / secretion Parathyroid Neoplasms / secretion* Phenylalanine / pharmacology Receptors, Calcium-Sensing / physiology |
| Chemical | |
Reg. No./Substance:
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0/Amino Acids; 0/Parathyroid Hormone; 0/Receptors, Calcium-Sensing; 63-91-2/Phenylalanine; 7440-70-2/Calcium |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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