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Thyrotropin (TSH)-induced receptor internalization in nonthyroidal cells transfected with a human TSH-receptor

N E Heldin1, B Gustavsson, A Hermansson

  • 1Department of Pathology, University Hospital, Uppsala, Sweden.

Endocrinology
|May 1, 1994
PubMed

Insights

Thyroid-stimulating hormone (TSH) desensitization occurred in NIH 3T3 cells expressing TSH receptors (TSHR), but not CHO cells. This suggests TSHR down-regulation causes homologous desensitization.

Area of Science:

  • Endocrinology
  • Molecular Biology
  • Cell Biology

Background:

  • Thyroid-stimulating hormone (TSH) regulates thyroid function through its receptor (TSHR).
  • Cellular responses to TSH can be modulated by receptor desensitization.
  • Understanding TSHR desensitization mechanisms is crucial for thyroid research.

Purpose of the Study:

  • To investigate TSH-induced desensitization in nonthyroidal cells expressing functional TSHR.
  • To compare desensitization in different cell lines (CHO and NIH 3T3) transfected with human TSHR.
  • To elucidate the molecular mechanisms underlying TSHR desensitization.

Main Methods:

  • Stable transfection of Chinese hamster ovary (CHO) and mouse NIH 3T3 cells with human TSHR cDNA.
  • Stimulation of transfected cells with varying concentrations and durations of TSH.
  • Measurement of TSH-induced cyclic AMP (cAMP) production.
  • Assessment of [125I]TSH binding to TSHR.
  • Investigation of forskolin's effect on desensitization.
  • Analysis of TSHR internalization via [125I]TSH incubation.

Main Results:

  • NIH-TSHR cells exhibited decreased sensitivity to TSH stimulation, reduced cAMP production, and diminished [125I]TSH binding within 1 hour.
  • Desensitization in NIH-TSHR cells was TSH-specific and not mimicked by forskolin, indicating a cAMP-independent pathway.
  • CHO-TSHR cells did not show desensitization or reduced TSH binding, potentially due to higher receptor turnover and more efficient ligand internalization.
  • Homologous desensitization in NIH-TSHR cells was linked to ligand-induced TSHR down-regulation.

Conclusions:

  • Homologous desensitization of TSHR occurs in NIH 3T3 cells and is mediated by ligand-induced receptor down-regulation.
  • Cell-specific differences in TSHR desensitization may relate to receptor internalization and turnover rates.
  • These findings provide insights into the regulation of TSHR signaling in nonthyroidal cells.

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