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TSH Receptor Interaction with the Extracellular Matrix: Role on Constitutive Activity and Sensitivity to Hormonal Stimulation

Institut National de la Santé et de la Recherche Médicale Unité135, Hormones, Gènes et Reproduction, Hôpital de Bicêtre, 94275 Le Kremlin-Bicêtre, France

Address all correspondence and requests for reprints to: Nicolae Ghinea, Ph.D., Institut National de la Santé et de la Recherche Médicale Unité 135, Centre Hospitalier Universitaire de Bicêtre, 3eme niveau, 78 rue du Général Leclerc, 94275 Le Kremlin-Bicêtre, France. E-mail: ghinea{at}infobiogen.fr.

Using immunocytochemistry, we have observed that the TSH receptor (TSHR) is concentrated at the leading edge of lamellipodia in both cultured human thyroid cells and in various transfected cells. This segregation of the receptor is due to its interaction with extracellular matrix (ECM) and specially with fibronectin. The TSHR, which interacts with the ECM, is known to undergo cleavage by a matrix metalloprotease. The homologous LH receptor, which does not interact with ECM, is not cleaved.

The attachment to the ECM modifies the functional properties of the receptor: it increases adenylate cyclase stimulation by hormone, whereas PLC stimulation is not modified. Furthermore, the constitutive activity of the TSHR is only observed in attached cells, suggesting that it is dependent on TSHR interaction with the ECM. Thus, aside from its classical properties of hormone binding and signalization through G proteins, the TSHR is also involved in cell-matrix interactions, which modulate its functional properties.

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