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Inhibition of Thyrotropin-Induced Growth of Rat Thyroid Cells, FRTL-5, by Immunoglobulin G From Patients with Primary Myxedema^*

YASUHIRO IIDA, JUNJI KONISHI, KANJI KASAGI, TAKASHI MISAKI, KEISUKE ARAI, YASUTAKA TOKUDA and KANJI TORIZUKA

Department of Radiology and Nuclear Medicine, Kyoto University School of Medicine Sakyo-ku, Kyoto 606, Japan

We studied thyroid growth-blocking activity in immunoglobulin G (IgG) fractions of serum from 24 patients with primary myxedema, 24 patients with goitrous Hashimoto’s thyroiditis, and 18 normal subjects by measuring the ability of their IgG to inhibit TSH-induced [³H]thymidine incorporation into DNA in a rat thyroid cell line, FRTL-5. Both groups of patients were receiving T₄ when studied. [³H]Thymidine incorporation induced by 0.1 mU/ml bovine TSH was significantly inhibited by the addition of 2 mg/ml IgG from patients with primary myxedema (P < 0.01), while it was not affected by IgG from the normal subjects or 23 of the 24 patients with goitrous Hashimoto’s thyroiditis. IgG from patients with primary myxe-dema also inhibited the [³H]thymidine incorporation induced by Graves’ IgG, but not that induced by forskolin, cholera toxin, (Bu)₂cAMP or phorbol-12-myristate-13-acetate. The inhibition of TSH-induced [³H]thymidine incorporation by IgGs from patients with primary myxedema was significantly correlated with their inhibitory activities against both TSH-induced cAMP generation and TSH binding (P < 0.001). These data indicate that these growth-blocking antibodies are directed against the TSH receptor and might be one of the causes of the thyroid atrophy in patients with primary myxedema.

^* This work was supported by Grant 61770792 from the Ministry of Education, Science, and Culture and a Research Grant for Intractable Diseases from the Ministry of Health and Welfare, Japan.

To whom requests for reprints should be addressed.

Received May 15, 1986.