Abstract
β-Arrestins mediate agonist dependent desensitization of G protein-coupled receptors. Somatic TSH receptor mutations were identified in the majority of hot thyroid nodules. When transiently overexpressed in COS 7 cells these mutations resulted in constitutive activation of the cAMP pathway. However, the in vivo mechanisms and the in vivo desensitization of these TSH receptor mutations are unknown. Moreover, constitutively activated β-adrenergic receptors are known to be constitutively desensitized. Therefore, we investigated the expression of β-arrestins in toxic thyroid nodules (TTNs) with and without somatic TSH receptor mutation and in cold thyroid nodules (CTNs) by Western blotting and ELISA. Expression of β-arrestin 2 was increased in all TTNs while β-arrestin 2 expression was decreased in CTNs compared to their corresponding surrounding tissue. The mean β-arrestin 1 expression was unchanged in the cytosol of TTNs, in membranes and cytosol of CTNs and decreased in the membranes of TTNs compared to their surrounding tissue. Transient coexpression of β-arrestins 1 or 2 with the TSH receptor in HEK 293 cells and subsequent determination of cAMP showed that in vitro both β-arrestins interact with the TSH receptor and are able to desensitize the receptor. The increased β-arrestin 2 expression in TTNs and the desensitization of the TSH receptor by β-arrestin 2 in vitro suggest that the β-arrestin 2 expression is cAMP dependent and that β-arrestin 2 very likely desensitizes the constitutively activated TSH receptor in toxic thyroid nodules.
Published Version (
Free)
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call