Document Detail


Thyrotropin (TSH)-induced receptor internalization in nonthyroidal cells transfected with a human TSH-receptor complementary deoxyribonucleic acid.
MedLine Citation:
PMID:  8156904     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
TSH-induced desensitization was studied in nonthyroidal cells expressing functionally active TSH receptors (TSHR). Chinese hamster ovary (CHO) cells and mouse NIH 3T3 cells were stably transfected with a human TSHR cDNA. Stimulation of the CHO-TSHR and NIH-TSHR cells with 10 mU/ml TSH resulted in a decreased sensitivity to a second TSH stimulation only in the NIH-TSHR cells. A decrease in TSH-induced cAMP was present within 1 h and coincided with a decreased binding of [125I]TSH. The half-maximal effect was observed after a 3- to 4-h stimulation with TSH, and exposure of cells to TSH for 20 h led to a 70-80% inhibition of cAMP formation. After withdrawal of TSH, cells regained full responsiveness to TSH after 6 h. Moreover, the desensitization effect observed in NIH-TSHR cells was not mimicked by forskolin and, therefore, was not mediated by cAMP. Stimulation of the CHO-TSHR cells with TSH did not result in a desensitization toward a second TSH stimulation, nor did it reduce the binding of [125I]TSH. This difference between the two cell lines might be explained by a higher turnover rate of receptors in the CHO cells. Indeed, incubation of cells with [125I]TSH showed a more efficient internalization of ligand in the CHO-TSHR cells compared to the NIH-TSHR cells. In summary, the homologous desensitization observed in TSHR-transfected NIH 3T3 cells appears to be the result of ligand-induced receptor down-regulation.
Authors:
N E Heldin; B Gustavsson; A Hermansson; B Westermark
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Endocrinology     Volume:  134     ISSN:  0013-7227     ISO Abbreviation:  Endocrinology     Publication Date:  1994 May 
Date Detail:
Created Date:  1994-05-16     Completed Date:  1994-05-16     Revised Date:  2006-11-15    
Medline Journal Info:
Nlm Unique ID:  0375040     Medline TA:  Endocrinology     Country:  UNITED STATES    
Other Details:
Languages:  eng     Pagination:  2032-6     Citation Subset:  AIM; IM    
Affiliation:
Department of Pathology, University Hospital, Uppsala, Sweden.
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MeSH Terms
Descriptor/Qualifier:
3T3 Cells
Animals
CHO Cells
Cricetinae
Cyclic AMP / metabolism
DNA, Complementary / genetics*
Endocytosis
Genetic Vectors
Humans
Kinetics
Mice
Receptors, Thyrotropin / drug effects,  genetics,  metabolism*
Simian virus 40 / genetics
Thyroid Neoplasms
Thyrotropin / metabolism,  pharmacology*
Transfection*
Tumor Cells, Cultured
Chemical
Reg. No./Substance:
0/DNA, Complementary; 0/Receptors, Thyrotropin; 60-92-4/Cyclic AMP; 9002-71-5/Thyrotropin

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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