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TSH and thyroid stimulating antibodies (TSAb) activate thyroid adenylate cyclase through different pathways
Acta Medica Scandinavica. Supplementum
|January 1, 1979
Summary
Thyroid stimulating antibodies (TSAb) and thyrotropin (TSH) activate adenylate cyclase differently in Graves' disease. These distinct pathways in the plasma membrane suggest unique mechanisms of thyroid stimulation.
Area of Science:
- Endocrinology
- Molecular Biology
- Immunology
Background:
- Thyrotropin (TSH) is the primary regulator of thyroid function.
- Thyroid stimulating antibodies (TSAb) are implicated in Graves' disease pathogenesis.
- Adenylate cyclase mediates cellular responses to TSH and TSAb.
Purpose of the Study:
- To investigate the distinct mechanisms of adenylate cyclase activation by TSH and TSAb in human thyroid homogenates.
- To compare the activation patterns, dose-responses, and subcellular localization of TSH- and TSAb-sensitive adenylate cyclase.
Main Methods:
- Stimulation of human thyroid homogenates with purified TSH and TSAb.
- Measurement of adenylate cyclase activity.
- Analysis of subcellular fractions.
- Assessment of cortisol's effect on enzyme activity.
Main Results:
- TSAb exhibited variable activation patterns and lag phases, differing from TSH.
- TSH and TSAb showed mutually inhibitory effects on adenylate cyclase.
- Cortisol modulated TSAb-induced, but not TSH-induced, adenylate cyclase activity.
- TSH-sensitive and TSAb-sensitive adenylate cyclase did not co-purify in subcellular fractions.
Conclusions:
- TSH and TSAb activate thyroid adenylate cyclase through distinct pathways within the plasma membrane.
- These findings elucidate the molecular basis for differential thyroid stimulation in Graves' disease.
- The data suggest separate receptor-mediated signaling cascades for TSH and TSAb.