title: Inhibition of thyrotropin-stimulated iodide uptake in FRTL-5 thyroid cells by crude immunoglobulin fractions from patients with goitrous and atrophic autoimmune thyroiditis.
abstract: We studied the effects of crude immunoglobulin (Ig) fractions of serum from patients with goitrous and atrophic autoimmune thyroiditis on TSH-, thyroid-stimulating immunoglobulin (TSI)-, forskolin-, and dibutyryl cAMP-stimulated 125I uptake by FRTL-5 thyroid cells. TSH-stimulated 125I uptake was inhibited by the Ig fractions from 15 patients with atrophic thyroiditis who had serum TSH binding inhibitor Igs (TBII), 10 (62.5%) of 16 TBII-negative patients with atrophic thyroiditis, 7 (43.8%) of 16 hypothyroid patients with goitrous thyroiditis who had no TBII activity, and only 2 (15.4%) of 13 euthyroid patients with goitrous thyroiditis who were negative for TBII. The mean inhibition of TSH-stimulated 125I uptake produced by the crude Igs from the former 3 groups of hypothyroid patients was statistically significant (P less than 0.001, P less than 0.001, and P less than 0.01, respectively) and correlated closely with the ability of the Ig fractions to inhibit TSI-stimulated 125I uptake (r = 0.882) and TSH-stimulated cAMP accumulation (r = 0.929). The inhibition of TSH- or TSI-stimulated 125I uptake by Ig samples containing TBII correlated significantly with the TBII activities. On the other hand, in the presence of Igs from TBII-negative hypothyroid patients, the inhibition of TSH-stimulated 125I uptake correlated significantly with that of forskolin-stimulated 125I uptake (r = 0.685). Although 6 (12.8%) of 47 Ig samples from hypothyroid patients inhibited dibutyryl cAMP-stimulated 125I uptake, the activities were marginal. These findings suggest that at least 2 types of antibodies are involved in the inhibition of TSH- or TSI-stimulated 125I uptake: 1 being a competitive inhibitor of TSH binding to its receptors, and another exerting influence on a step subsequent to TSH or TSI binding, presumably through adenylate cyclase inhibition.
mesh_terms: D003994:Bucladesine / Q000494:pharmacology; D002478:Cells, Cultured; D005576:Colforsin / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D006042:Goiter / Q000378:metabolism*; D006801:Humans; D007074:Immunoglobulin G / Q000494:pharmacology; D007136:Immunoglobulins / Q000494:pharmacology*; D018828:Immunoglobulins, Thyroid-Stimulating; D007454:Iodides / Q000493:pharmacokinetics*; D013961:Thyroid Gland / Q000378:metabolism*; D013967:Thyroiditis, Autoimmune / Q000378:metabolism*; D013972:Thyrotropin / Q000037:antagonists & inhibitors / Q000494:pharmacology*
chemical_list: D007074:Immunoglobulin G; D007136:Immunoglobulins; D018828:Immunoglobulins, Thyroid-Stimulating; D007454:Iodides; D005576:Colforsin; D003994:Bucladesine; D013972:Thyrotropin