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Thyroid hormone export regulates cellular hormone content and response

R C Ribeiro1, R R Cavalieri, N Lomri

  • 1Department of Medicine, University of California, San Francisco, California 94143-0540, USA.

The Journal of Biological Chemistry
|July 19, 1996
PubMed
Summary
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Thyroid hormone (TH) resistance in cancer cells is caused by enhanced TH extrusion. This process, potentially mediated by P-glycoproteins, lowers intracellular TH levels and impacts hormone action in various mammalian cells.

Area of Science:

  • Endocrinology
  • Cell Biology
  • Molecular Pharmacology

Background:

  • Thyroid hormone (TH) action is regulated by intracellular free hormone concentrations.
  • Understanding the mechanisms controlling intracellular TH levels is crucial for comprehending TH resistance.

Purpose of the Study:

  • To investigate the role of enhanced TH extrusion in causing TH resistance in hepatoma cells.
  • To identify the potential mechanisms and mediators of TH extrusion and resistance.

Main Methods:

  • Studied TH extrusion using a saturable, cold-sensitive mechanism in hepatoma cells.
  • Investigated the role of multidrug resistance P-glycoproteins (P-gp) in TH transport.
  • Assessed the effect of verapamil on TH extrusion and resistance.
  • Examined verapamil-inhibitable TH efflux in primary hepatocytes, cardiocytes, and fibroblasts.

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Main Results:

  • Enhanced TH extrusion was found to lower intracellular TH levels and induce TH resistance in hepatoma cells.
  • Hepatoma cells overexpressing P-gp showed blunted TH extrusion and resistance in the presence of verapamil, suggesting P-gp mediation.
  • Verapamil-inhibitable TH efflux was also observed in primary hepatocytes, cardiocytes, and fibroblasts.

Conclusions:

  • TH extrusion is a significant mechanism that modulates intracellular TH availability and action in mammalian cells.
  • P-glycoproteins may play a role in mediating TH extrusion and resistance.
  • These findings have implications for understanding TH action and resistance in various physiological and pathological contexts.