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Thyroid hormone beta receptor mutation causes renal dysfunction and impairment of ClC-2 chloride channel expression

Debora Dos Santos Ornellas1, Aline Cristina Gomes, Leticia Aragao Santiago

  • 1Laboratory of Molecular and Cellular Physiology, Carlos Chagas Filho Biophysics Institute, Federal University of Rio de Janeiro, Rio de Janeiro, Brazil.

Cellular Physiology and Biochemistry : International Journal of Experimental Cellular Physiology, Biochemistry, and Pharmacology
|August 28, 2010
PubMed
Abstract

Insights

Thyroid hormone resistance (RTH) in mice with a TR-beta mutation affects kidney function and ClC-2 chloride channel expression. Thyroid hormone modulates ClC-2 gene transcription through the TR-beta receptor pathway.

Area of Science:

  • Endocrinology
  • Nephrology
  • Molecular Biology

Background:

  • Resistance to thyroid hormone (RTH) is caused by mutations in the thyroid hormone receptor beta (TR-beta) gene.
  • The Delta337T mutation in TR-beta mimics RTH syndrome in mice, impacting renal function.

Purpose of the Study:

  • Investigate the role of the TR-beta receptor in thyroid hormone modulation of the ClC-2 channel in mouse kidneys.
  • Analyze the impact of RTH on renal electrolyte handling and ClC-2 expression.

Main Methods:

  • Studied renal RNA and protein expression of ClC-2 in normal and Delta337T mutant mice using RT-PCR and Western blot.
  • Assessed renal function via urinary electrolyte excretion analysis.
  • Examined ClC-2 promoter activity in immortalized renal proximal tubule cells in vitro.

Main Results:

  • RTH mice exhibited altered fractional excretion of sodium and chloride.
  • ClC-2 mRNA and protein expression were reduced by 40% in mutant mouse kidneys.
  • Thyroid hormone stimulated ClC-2 promoter activity in a dose-dependent manner in vitro.

Conclusions:

  • Thyroid hormone is crucial for electrolyte balance in the nephron.
  • The TR-beta receptor pathway mediates thyroid hormone's effect on renal ClC-2 gene transcription.

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