Autoantibody stimulation of the human thyrotropin receptor: regulation of adenylate cyclase activity, thyroglobulin and thyroid peroxidase mRNA levels in primary cultures of Graves' thyroid tissue.
The effects of immunoglobulin preparations from hyperthyroid Graves' disease patients on primary cultures of thyroid cells have been studied at the mRNA level. Autoantibodies to the thyrotropin (TSH) receptor from these patients, which had been initially characterized by their ability to stimulate adenylate cyclase and inhibit the binding of radiolabelled TSH to thyroid membrane preparations, were studied for their effects on thyroglobulin and thyroid peroxidase mRNA levels. Incubation of thyroid cells with TSH receptor autoantibodies from different Graves' disease patients for 48 h led to time- and dose-dependent increases in the levels of thyroid peroxidase and thyroglobulin mRNA in primary cultures of thyrocytes. The incomplete correlation between G protein-linked adenylate cyclase activation and thyroid mRNA elevation indicates the possibility of the involvement of alternative second messenger pathways in the regulation of thyroid cell function and differentiation.
Department of Medicine, King's College School of Medicine and Dentistry, London, UK.
K S
KS
Collison
J P
JP
Banga
P S
PS
Barnett
G C
GC
Huang
A M
AM
McGregor
D000262:Adenylyl Cyclases / Q000378:metabolism; D001323:Autoantibodies / Q000276:immunology*; D015152:Blotting, Northern; D002478:Cells, Cultured; D004306:Dose-Response Relationship, Immunologic; D015870:Gene Expression; D006111:Graves Disease / Q000503:physiopathology*; D006801:Humans; D066298:In Vitro Techniques; D007453:Iodide Peroxidase / Q000235:genetics; D012333:RNA, Messenger / Q000235:genetics; D011989:Receptors, Thyrotropin / Q000276:immunology*; D015398:Signal Transduction; D013954:Thyroglobulin / Q000235:genetics; D013961:Thyroid Gland / Q000503:physiopathology*; D013972:Thyrotropin / Q000494:pharmacology; D013997:Time Factors
D001323:Autoantibodies; D012333:RNA, Messenger; D011989:Receptors, Thyrotropin; D013972:Thyrotropin; D013954:Thyroglobulin; D007453:Iodide Peroxidase; D000262:Adenylyl Cyclases