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    Role of the adenylate cyclase-cAMP system on TSH-stimulated thyroid cell growth

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    : TSH is a trophic factor for cultured rat thyroid cells (FRTL-5). In the present study we have investigated the mechanism by which TSH promotes cell growth and evaluated the possible role of the adenylate cyclase (AC)-cAMP system in this process. The mitogenic activity of several agents was evaluated by measuring their effect on cell number or 3H-thymidine incorporation into DNA. Forskolin and cholera toxin, two potent and specific activators of the AC, induced a dose dependent increase of 3H-thymidine incorporation. The maximal stimulation, observed at concentrations of 10 microM and 10 ng/ml, respectively, was beta 80% of that obtained with optimal concentrations of TSH. A similar effect was obtained with a Graves' IgG preparation (0.2 mg/ml) able to stimulate the thyroid AC or with 3-isobutyl-1-methyl-xanthine (IBMX, 0.5 mM), a phosphodiesterase inhibitor. 8-bromo cAMP (0.5 mM), a cAMP analog, also stimulated 3H-thymidine incorporation, and its potency was approximately 60% of that of TSH. Similar results were obtained when the mitogenic activity of these compounds was evaluated by cell number. Norepinephrine (NE, 10 microM), although devoid of AC stimulatory activity in these cells, also stimulated 3H-thymidine incorporation, but its potency was only 20-30% of that of TSH. Indomethacin (100 microM), an inhibitor of phospholipid and arachidonic acid metabolism, was able to inhibit the stimulatory effect of NE (84%), and to a lesser extent of TSH (63%) and cholera toxin, had minor effect on forskolin (24%), IBMX (16%) and Graves' IgG (8%), and no effect on 8-bromo cAMP.(ABSTRACT TRUNCATED AT 250 WORDS

    Interference of thyroglobulin in TSAb detection by radio-receptor assay

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    Sir: Dr. Schleusener et al. recently reported in this Journal (1) that thyroid-stimulating antibody (TSAb) determina- tions in Graves' patients could be useful in predicting relapse after antithyroid drug withdrawal. TSAb is present in serum of many untreated Graves' patients, but the percent of positive patients differs among the different series reported (1-6). These dis- crepancies do not appear justified by the radio- receptor assay methods employed. Human thyroglobulin (hTg) is found in serum of many normal subjects in an average concentration of about 5 ng/ml, its level raises up to >150 ng/ ml in untreated Graves' patients (7), decreases with antithyroid drug treatment (8), but it is found still elevated in those pa- tients who relapse after drug withdrawal (8). Recently one of us (9) reported that physiological amounts of thyroglobulin can interfere in the binding of TSH to human thyroid plasma membrane
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