Synthetic peptides, representing specific portions of the α-subunit of the human glycoprotein hormones, can inhibit both the binding of labeled TSH to thyroid membranes and adenylate cyclase stimulation by TSH in vitro. The same synthetic peptides (α26–46 and α31–45) significantly (P < 0.05) inhibited the adenylate cyclase-stimulating activity of thyroidstimulating immunoglobulins (TSI) from 10 patients with hyperthyroid Graves’ disease. Peptide α26–46 was the most potent, resulting in 79.1 ± 8.8% (± SE) inhibition at 133 μg/mL, while peptide α31–45 inhibited TSI activity by 36.3 ± 5.2%. Peptides α61–75 and α81–92, that had only minimal ability to inhibit TSH-medicated cAMP generation, did not significantly inhibit TSI activity. The inhibitory action of α26–46 was dose dependent, and a significant negative correlation was found between the maximum TSI activity of the serum sample and the inhibition achieved by the synthetic peptide, suggesting that differences in TSI affinity and/or titer may account for the variable inhibitory activity of the peptides. These results suggest that TSI interact with the TSH receptor at the site that recognizes the portion of the TSH α-subunit represented by the synthetic peptide α26–46 and, thus, support the concept that the TSHbinding site of the TSH receptor is the site of antigen binding between TSI and the thyroid cell.
ASJC Scopus subject areas
- Endocrinology, Diabetes and Metabolism
- Clinical Biochemistry
- Biochemistry, medical