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L-amino acids regulate parathyroid hormone secretion.

Arthur D Conigrave1, Hee-Chang Mun, Leigh Delbridge

  • 1School of Molecular and Microbial Biosciences, University of Sydney, New South Wales 2006, Australia. a.conigrave@mmb.usyd.edu

The Journal of Biological Chemistry
|July 6, 2004
PubMed
Summary

L-amino acids, not just calcium and magnesium, are key regulators of parathyroid hormone (PTH) secretion. These amino acids activate the calcium-sensing receptor (CaR) in parathyroid cells, reducing PTH release and influencing calcium metabolism.

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Area of Science:

  • Endocrinology
  • Cell Biology
  • Metabolic Regulation

Background:

  • Parathyroid hormone (PTH) secretion is primarily regulated by extracellular calcium (Ca2+) and magnesium (Mg2+) ions via the Ca2+-sensing receptor (CaR).
  • The role of other physiological molecules in modulating PTH secretion through CaR activation remains an area of active investigation.

Purpose of the Study:

  • To investigate the role of l-amino acids as direct regulators of PTH secretion.
  • To determine if l-amino acids activate the CaR and influence PTH release in human parathyroid cells.

Main Methods:

  • Experiments utilized normal human parathyroid cells.
  • Assays measured Ca2+ mobilization and PTH secretion in response to various l-amino acids and CaR agonists.
  • Concentrations of Ca2+, Mg2+, and amino acids were physiologically relevant.

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Main Results:

  • L-amino acids, particularly aromatic and aliphatic types, activated the CaR and mobilized intracellular Ca2+ in parathyroid cells.
  • Specific l-amino acids (l-Trp, l-Phe, l-His, l-Ala, l-Glu) demonstrated varying potencies in CaR activation.
  • Physiological concentrations of l-amino acids and plasma-like amino acid mixtures acutely and reversibly suppressed PTH secretion, comparable to elevated Ca2+ levels.

Conclusions:

  • L-amino acids are identified as novel, physiological regulators of PTH secretion.
  • Activation of endogenous CaRs by l-amino acids directly inhibits PTH release.
  • These findings suggest a significant role for amino acids in whole-body calcium homeostasis.