Effect of Iodine Enrichment in Vitro on the Adenylate Cyclase-Adenosine 3′,5′ Monophosphate System inThyroid Glands from Normal Subjects and Patients with Graves’ Disease*

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Abstract
We have studied the in vitro effect of iodineenrichment of the adenylate cyclase-cAMP system in thyroidtissue from patients with normal thyroid function and those withGraves′ disease. Tissue was obtained from patients who had notbeen treated with iodide preoperatively. Thyroid tissues werepreincubated in Krebs-Ringer bicarbonate buffer with or without10−4 M Nal at 37 C for 3 h, and cAMP responsiveness to TSH(50 mU/ml) in slices and TSH- or 5′-guanylylimidodiphosphate(Gpp(NH)p)-stimulated adenylate cyclase activityin plasma membranes was studied. At the time of preincubationwith Nal, 0.3 μCi 131I was added to measure organic 131I uptake.Although iodide did not affect cAMP responsiveness to TSH innormal thyroid tissue, the increase of cAMP in response to TSH was inhibited by iodide in thyroid tissue from patients with Graves’ disease. TSH- or Gpp(NH)p-stimulated adenylate cyclaseactivity also was blunted by iodide in plasma membrane:from Graves’ thyroid tissue but not in plasma membranes fromnormal thyroid tissue. In vitro organic 131I uptake with 10−4 MNal was lower in thyroid slices from patients with Graves’disease than in normal thyroid slices, while with 10−7 M Nal,uptake was higher in thyroid slices from patients with Grave’disease than in normal thyroid slices. These results suggest that the adenylate cyclase-cAMP systern of Graves’ thyroid is moresusceptible to iodide than is thai,of normal tissue. The susceptibility to iodide of thyroid glandsfrom patients with Graves’ disease is not due to the higher iodineuptake in Graves glands;rather, iodide appears to exert its effeci.on a site between the purine nucleotide regulatory unitand thecatalytic unit in the adenylate cyclase-cAMP system. (J ClinEndocrinol Metab50: 1066, 1980)

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