Expression of beta-arrestins in toxic and cold thyroid nodules

beta -Arrestins mediate agonist dependent desensitization of G protein-coup led receptors. Somatic TSH receptor mutations were identified in the majori ty of hot thyroid nodules. When transiently overexpressed in COS 7 cells th ese mutations resulted in constitutive activation of the cAMP pathway. Howe ver, the in vivo mechanisms and the in vivo desensitization of these TSH re ceptor mutations are unknown. Moreover, constitutively activated beta -adre nergic receptors are known to be constitutively desensitized. Therefore, we investigated the expression of beta -arrestins in toxic thyroid nodules (T TNs) with and without somatic TSH receptor mutation and in cold thyroid nod ules (CTNs) by Western blotting and ELISA. Expression of beta -arrestin 2 w as increased in all TTNs while beta -arrestin 2 expression was decreased in CTNs compared to their corresponding surrounding tissue. The mean beta -ar restin 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 su rrounding tissue. Transient coexpression of beta -arrestins 1 or 2 with the TSH receptor in HEK 293 cells and subsequent determination of cAMP showed that in vitro both beta -arrestins interact with the TSH receptor and are a ble to desensitize the receptor. The increased beta -arrestin 2 expression in TTNs and the desensitization of the TSH receptor by beta -arrestin 2 in vitro suggest that the beta -arrestin 2 expression is cAMP dependent and th at beta -arrestin 2 very likely desensitizes the constitutively activated T SH receptor in toxic thyroid nodules. (C) 2000 Federation of European Bioch emical Societies. Published by Elsevier Science B.V. All rights reserved.