TSH and Thyroid Stimulating Antibodies (TSAb) Activate Thyroid Adenylate Cyclase through Different Pathways

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Abstract
Adenylate cyclase activity in human thyroid homogenates was studied after stimulation with thyrotropin (TSH) and thyroid stimulating antibodies (TSAb). TSAb prepared from different patients with Graves'' disease showed different adenylate cyclase activation patterns and a lag phase was frequently observed. TSH and TSAb appeared to cause mutually inhibitory activation of thyroid adenylate cyclase. The maximal adenylate cyclase activation was higher with TSH than with TSAb, but this could possibly be due to contamination of TSAb preparations with an adenylate cyclase inhibitor. There was no absolute copurification of TSH sensitive and TSAb sensitive adenylate cyclase in various subcellular fractions of thyroid homogenate. Incubation of thyroid homogenate with cortisol caused a dose dependent decrease in the adenylate cyclase response to TSAb whereas the response to TSH was either increased or unchanged. TSH and TSAb activate thyroid adenylate cyclase through different pathways in the plasma membrane.