Gi alpha-1 expression in the human thyroid is regulated by TSH: loss of regulation in thyroid autonomous adenoma.
The molecular mechanisms underlying the development of endocrine active thyroid tumors are poorly understood. These tumors produce excess thyroid hormone, which then suppresses TSH (thyroid stimulating hormone) production. In the present report, we show that the expression of Gi alpha-1 is under control of TSH in the normal human thyroid. In contrast Gi alpha-1 escapes TSH control in autonomous adenoma and thus is constitutively expressed. Since receptor-mediated activation of Gi controlled pathways is known to elicit a proliferative response in several cell types, we propose that in thyroid adenomas the unregulated constitutive expression of Gi alpha-1 is causally related to the autonomous growth.
Selzer
E
E
Institute of Pharmacology, Vienna.
Schiferer
A
A
Hermann
M
M
Grubeck-Loebenstein
B
B
Freissmuth
M
M
D000236:Adenoma / Q000201:enzymology / Q000378:metabolism / Q000503:physiopathology*; D000246:Adenosine Diphosphate Ribose / Q000378:metabolism; D000262:Adenylyl Cyclases / Q000378:metabolism; D001345:Autoradiography; D002455:Cell Division / Q000187:drug effects; D004591:Electrophoresis, Polyacrylamide Gel; D019204:GTP-Binding Proteins / Q000096:biosynthesis*; D006801:Humans; D015151:Immunoblotting; D008970:Molecular Weight; D015398:Signal Transduction / Q000187:drug effects; D013961:Thyroid Gland / Q000187:drug effects / Q000201:enzymology / Q000378:metabolism*; D013964:Thyroid Neoplasms / Q000201:enzymology / Q000378:metabolism / Q000503:physiopathology*; D013972:Thyrotropin / Q000494:pharmacology*; D010566:Virulence Factors, Bordetella / Q000494:pharmacology
D010566:Virulence Factors, Bordetella; D000246:Adenosine Diphosphate Ribose; D013972:Thyrotropin; D019204:GTP-Binding Proteins; D000262:Adenylyl Cyclases