Modulation of the biological activity of thyrotrophin by anti-human thyrotrophin monoclonal antibodies.
The mechanism by which monoclonal antibodies enhance the biological activity of a number of hormones is poorly understood. One such antibody (GC73), which binds to human but not bovine TSH, enhances the bioactivity of human TSH in vivo. We have investigated whether GC73 enhancement of TSH bioactivity involves potentiation of hormone-receptor activation assessed by the cyclic AMP (cAMP) responses of both primary human thyrocyte cultures and a TSH-responsive human thyrocyte cell line (SGHTL-45). GC73 had no effect on basal cAMP production. In contrast to its enhancement of the bioactivity of human TSH in vivo, it markedly inhibited the cAMP response to 1 and 10 mU human TSH/ml in primary thyrocytes. This effect was dose-dependent with neutralization of the bioactivity of TSH occurring at 2 mg GC73/ml. GC73 had no effect on the bioactivity of bovine TSH. In contrast, a second anti-TSH monoclonal antibody (TC12), which binds to both human and bovine TSH, inhibited the bioactivity of both species of TSH. Similar results were obtained using SGHTL-45 cells, although the peak concentrations of cAMP were lower. We conclude that binding of GC73 to human TSH resulted in inhibition rather than enhancement of the in-vitro biological activity of human TSH. We suggest that GC73 enhancement of human TSH bioactivity seen in vivo does not result from a mechanism involving potentiation of receptor activation by human TSH.
Page
S R
SR
Department of Cellular and Molecular Sciences, St George's Hospital Medical School, London.
Taylor
A H
AH
Driscoll
W
W
Baines
M
M
Thorpe
R
R
Johnstone
A P
AP
Nussey
S S
SS
Whitley
G S
GS
D000911:Antibodies, Monoclonal / Q000378:metabolism*; D001682:Biological Availability; D002850:Chromatography, Gel; D000242:Cyclic AMP / Q000096:biosynthesis; D006801:Humans; D013961:Thyroid Gland / Q000166:cytology / Q000378:metabolism*; D013972:Thyrotropin / Q000378:metabolism*
D000911:Antibodies, Monoclonal; D013972:Thyrotropin; D000242:Cyclic AMP