RGS 2 expression is regulated by TSH and inhibits TSH receptor signaling.
OBJECTIVE
A new family of guanosine triphosphatase-activating proteins known as regulators of G protein signaling (RGS) has been found to regulate the desensitization of several G protein-coupled ligand-induced processes. The expression of nine RGS mRNAs was found in human thyroid tissue (RGS 2, 3, 5, 6, 9, 10, 12, 14 and 16). At present, little is known as to whether any of the RGS proteins play a role in TSH signaling.


METHODS
To explore the involvement of RGS proteins in the regulation of TSH receptor (TSHR) signal transduction, mRNA expression levels of the RGS proteins were analyzed after TSH stimulation of human thyroid primary cultures by real-time RT-PCR. Furthermore, the effects of RGS 2 expression on TSHR signaling (cAMP-, inositol-3-phosphate accumulation, TSHR cell surface expression) were studied in COS-7 cells.


RESULTS
Only RGS 2 mRNA was found to be regulated by TSH in thyroid primary cultures. Co-expression of RGS 2 and TSHR in COS-7 cells reduced the TSHR signaling via inositol-3-phosphate but not via cAMP after stimulation with TSH.


CONCLUSIONS
TSH-dependent RGS 2 mRNA expression and the suppression of TSH-G(q)alpha signaling by the overexpression of RGS 2 imply that RGS 2 is involved in TSHR-induced G(q) signal transduction.
Eszlinger
Markus
M
III Medical Department, University of Leipzig, Ph.-Rosenthal-Str. 27, D-04103 Leipzig, Germany.
Holzapfel
Hans-Peter
HP
Voigt
Carsten
C
Arkenau
Cord
C
Paschke
Ralf
R
D000818:Animals; D019556:COS Cells; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D006801:Humans; D020710:RGS Proteins / Q000235:genetics*; D012333:RNA, Messenger / Q000378:metabolism; D011989:Receptors, Thyrotropin / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects; D016606:Thyroid Nodule / Q000503:physiopathology*; D013972:Thyrotropin / Q000494:pharmacology*; D014407:Tumor Cells, Cultured
D020710:RGS Proteins; C087182:RGS2 protein, human; D012333:RNA, Messenger; D011989:Receptors, Thyrotropin; D013972:Thyrotropin