Document Detail


Adenomatous human parathyroid cells exhibit impaired sensitivity to L-amino acids.
MedLine Citation:
PMID:  19567535     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
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.
Authors:
H-C Mun; S C Brennan; L Delbridge; M Wilkinson; E M Brown; A D Conigrave
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Publication Detail:
Type:  Journal Article     Date:  2009-06-30
Journal Detail:
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:
Created Date:  2009-09-07     Completed Date:  2009-09-23     Revised Date:  2013-06-02    
Medline Journal Info:
Nlm Unique ID:  0375362     Medline TA:  J Clin Endocrinol Metab     Country:  United States    
Other Details:
Languages:  eng     Pagination:  3567-74     Citation Subset:  AIM; IM    
Affiliation:
School of Molecular and Microbial Biosciences, University of Sydney, New South Wales 2006, Australia.
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MeSH Terms
Descriptor/Qualifier:
Adenoma / 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:
0/Amino Acids; 0/Parathyroid Hormone; 0/Receptors, Calcium-Sensing; 63-91-2/Phenylalanine; 7440-70-2/Calcium
Comments/Corrections

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