TY - JOUR
T1 - The effects of synthetic α-subunit peptides on thyroid-stimulating immunoglobulin activity
AU - Morris, John C.
AU - Jiang, Nai Siang
AU - Hay, Ian D.
AU - Charlesworth, M. Cristine
AU - Mc cormick, Daniel J.
AU - Ryan, Robert J.
PY - 1988/10
Y1 - 1988/10
N2 - 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.
AB - 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.
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U2 - 10.1210/jcem-67-4-707
DO - 10.1210/jcem-67-4-707
M3 - Article
C2 - 2458377
AN - SCOPUS:0023714036
SN - 0021-972X
VL - 67
SP - 707
EP - 712
JO - Journal of Clinical Endocrinology and Metabolism
JF - Journal of Clinical Endocrinology and Metabolism
IS - 4
ER -