Aluminum posttranscriptional regulation of parathyroid hormone synthesis: a role for the calcium-sensing receptor

Kidney Int. 2005 Dec;68(6):2484-96. doi: 10.1111/j.1523-1755.2005.00724.x.


Background: Calcium regulates parathyroid hormone (PTH) gene expression by a posttranscriptional mechanism, as well as parathyroid gland growth through the activation of the calcium-sensing receptor. Aluminum decreases both parathyroid cell proliferation and PTH levels by an unknown mechanism.

Methods: To investigate the possible role of calcium-sensing receptor in the aluminum-induced PTH inhibition we used human embryonic kidney (HEK-293) cells transiently transfected with the human calcium-sensing receptor. We used a parathyroid gland tissue culture model to investigate whether the effect of aluminum in PTH mRNA was a transcriptional mechanism and also its possible role in calcium-sensing receptor expression.

Results: We found that Al activated the calcium-sensing receptor with higher efficiency than calcium, its biologic ligand. Aluminum inhibited PTH gene expression by a posttranscriptional mechanism, but only when low calcium is present in the medium. Finally, we found that aluminum is also able to decrease calcium-sensing receptor mRNA levels by a posttranscriptional mechanism; however, no effect was observed on calcium-sensing receptor protein.

Conclusion: These findings indicate that aluminum impairs parathyroid function through a calcium-like mechanism due to the lack of specificity of the calcium-sensing receptor. Additionally, aluminum decreases parathyroid calcium-sensing receptor mRNA levels, and the regulatory mechanism was posttranscriptional. These findings demonstrate for the first time a regulatory effect in the calcium-sensing receptor by one of its ligands.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aluminum Chloride
  • Aluminum Compounds / pharmacology*
  • Animals
  • Antibodies
  • Astringents / pharmacology*
  • Cell Division / drug effects
  • Cell Line
  • Chlorides / pharmacology*
  • Gene Expression Regulation / drug effects
  • Humans
  • Immunohistochemistry
  • In Vitro Techniques
  • Kidney / cytology
  • Male
  • Parathyroid Glands / cytology
  • Parathyroid Glands / drug effects*
  • Parathyroid Glands / physiology
  • Parathyroid Hormone / genetics*
  • Parathyroid Hormone / metabolism
  • RNA Processing, Post-Transcriptional / drug effects*
  • RNA, Messenger / metabolism
  • Rats
  • Rats, Wistar
  • Receptors, Calcium-Sensing / genetics
  • Receptors, Calcium-Sensing / immunology
  • Receptors, Calcium-Sensing / metabolism*
  • Transfection


  • Aluminum Compounds
  • Antibodies
  • Astringents
  • Chlorides
  • Parathyroid Hormone
  • RNA, Messenger
  • Receptors, Calcium-Sensing
  • Aluminum Chloride