TSH/IGF1 receptor crosstalk: Mechanism and clinical implications

Pharmacol Ther. 2020 May:209:107502. doi: 10.1016/j.pharmthera.2020.107502. Epub 2020 Feb 13.

Abstract

Increasing evidence of interdependence between G protein-coupled receptors and receptor tyrosine kinase signaling pathways has prompted reevaluation of crosstalk between these receptors in disease and therapy. Investigations into thyroid-stimulating hormone (TSH) and insulin-like growth factor 1 (IGF1) receptor crosstalk, and its application to the clinic have in particular shown recent progress. In this review, we summarize current insights into the mechanism of TSH/IGF1 receptor crosstalk. We discuss evidence that crosstalk is one of the underlying causes of TSHR-based disease and the feasibility of using combinations of TSH receptor and IGF1 receptor antagonists to increase the therapeutic index for the treatment of Graves' hyperthyroidism and Graves' ophthalmopathy.

Keywords: Graves' ophthalmopathy fibroblasts; Insulin-like growth factor 1 receptor; Receptor crosstalk; TSH receptor stimulating antibodies; Thyroid-stimulating hormone receptor.

Publication types

  • Research Support, N.I.H., Intramural
  • Review

MeSH terms

  • Animals
  • Autoantibodies / drug effects
  • Autoantibodies / metabolism
  • Graves Ophthalmopathy / drug therapy
  • Graves Ophthalmopathy / metabolism*
  • Hormone Antagonists / administration & dosage
  • Hormone Antagonists / metabolism
  • Humans
  • Receptor Cross-Talk / drug effects
  • Receptor Cross-Talk / physiology*
  • Receptor, IGF Type 1 / antagonists & inhibitors
  • Receptor, IGF Type 1 / metabolism*
  • Receptors, Thyrotropin / antagonists & inhibitors
  • Receptors, Thyrotropin / metabolism*
  • Thyrotropin / antagonists & inhibitors
  • Thyrotropin / metabolism*

Substances

  • Autoantibodies
  • Hormone Antagonists
  • IGF1R protein, human
  • Receptors, Thyrotropin
  • Thyrotropin
  • Receptor, IGF Type 1