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. 2018 Oct:2:29-33.
doi: 10.1016/j.coemr.2018.01.007. Epub 2018 Feb 5.

Thyroid Stimulating Hormone (TSH)/Insulin-like Growth Factor 1 (IGF1) Receptor Cross-talk in Human Cells

Christine C Krieger  1 , Sarah J Morgan  1 , Susanne Neumann  1 , Marvin C Gershengorn  1
Affiliations

Thyroid Stimulating Hormone (TSH)/Insulin-like Growth Factor 1 (IGF1) Receptor Cross-talk in Human Cells

Christine C Krieger et al. Curr Opin Endocr Metab Res. 2018 Oct.

Abstract

Thyroid stimulating hormone and insulin-like growth factor 1 receptors (TSHRs and IGF1Rs, respectively) interact leading to additive or synergistic stimulation of cellular responses. Recent findings provide evidence that the interaction between TSHRs and IGF1Rs is similar to that described for other G protein-coupled receptors and receptor tyrosine kinases. These types of interactions occur at or proximal to the receptors and are designated "receptor cross-talk." Herein, we describe our studies in human thyrocytes, human retro-orbital fibroblasts from Graves' orbitopathy patients and a model cell line that support the concept of TSHR/IGF1R cross-talk. We also discuss how receptor cross-talk is involved in stimulation by a monoclonal TSHR-stimulating antibody and how targeting both receptors may lead to novel treatments of Graves' orbitopathy.

Keywords: IGF1; TSH; receptor cross-talk.

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Figures

Figure 1
Figure 1. Effects of IGF1 on TSH-stimulated hyaluronan secretion by GOFs
Adapted from (13). TSH/IGF1 synergy in hyaluronan (HA) secretion was demonstrated by the effects of IGF1 to concentration-dependently (a) increase the potency of TSH and (b) cause a more than additive increase in efficacy of maximal doses of TSH.
Figure 2
Figure 2. Inhibition of TSH- and IGF1-stimulated HA secretion by TSHR antagonist C1 and IGF-1R antagonist linsitinib
Reprinted from (13). The TSHR inhibitor C1 fully inhibited TSH and partially inhibited IGF1 and TSH+IGF1 stimulation of HA secretion. The IGF1R inhibitor fully inhibited IGF1 and partially inhibited TSH and TSH+IGF1 stimulation. *P<0.03, **P<0.001
Figure 3
Figure 3. Effect of the monoclonal TSHR stimulatory antibody M22 on hyaluronan secretion in GOFs
Adapted from (13). M22 stimulated hyaluronan secretion (HA) in a biphasic manner. The higher potency (lower concentrations of M22) phase was inhibited by the IGF1R inhibitor linsitinib whereas the lower potency (higher concentrations of M22) was not inhibited. A TSHR antagonist inhibited both phases of M22 stimulation (not shown here).
Figure 4
Figure 4. Proposed model for M22-initiated TSHR/IGF1R cross-talk in Graves’ orbital fibroblasts
Adapted from [18]. The M22 concentration-response of hyaluronan (HA) secretion is shown on the left. Both phases of the M22 response are initiated by binding only to TSHR. Phase 1 is the high potency (low concentrations) phase and phase 2 is the low potency (high concentrations) phase. Within phase 1, M22 stimulation is dependent on IGF1 receptors (white arrows) whereas in phase 2 M22 stimulation is independent of IGF1R.
See this image and copyright information in PMC

References

    1. Delcourt N, Bockaert J, Marin P. GPCR-jacking: from a new route in RTK signalling to a new concept in GPCR activation. Trends Pharmacol Sci. 2007;28:602–607. - PubMed
    1. Pyne NJ, Pyne S. Receptor tyrosine kinase-G-protein-coupled receptor signalling platforms: out of the shadow? Trends Pharmacol Sci. 2011;32:443–450. - PubMed
    1. Rozengurt E, Sinnett-Smith J, Kisfalvi K. Crosstalk between insulin/insulin-like growth factor-1 receptors and G protein-coupled receptor signaling systems: a novel target for the antidiabetic drug metformin in pancreatic cancer. Clin Cancer Res. 2010;16:2505–2511. - PMC - PubMed
    1. Tramontano D, Cushing GW, Moses AC, Ingbar SH. Insulin-like growth factor-I stimulates the growth of rat thyroid cells in culture and synergizes the stimulation of DNA synthesis induced by TSH and Graves'-IgG. Endocrinology. 1986;119:940–942. - PubMed
    1. Santisteban P, Kohn LD, Di Lauro R. Thyroglobulin gene expression is regulated by insulin and insulin-like growth factor I, as well as thyrotropin, in FRTL-5 thyroid cells. J Biol Chem. 1987;262:4048–4052. - PubMed

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