On the Mechanism of Inhibition by Iodine of the Thyroid Adenylate Cyclase Response to Thyrotropic Hormone

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Abstract
Rats maintained on a low-I diet were hypophysectomized, and their diet was then enriched with iodide. Cyclic AMP (cAMP) concentrations achieved in their thyroids following in vitro TSH [thyrotropin] stimulation were significantly lower than those in the thyroids of control animals that did not receive dietary iodide enrichment. The addition of 0.1% methimazole (MMI) or 1% KClO4 to the diet abolished this inhibitory effect of iodide. The administration of triiodothyronine in the diet did not reproduce the inhibitory effect of iodide. The effect of iodide in vitro on the thyroid cAMP response to TSH was investigated using paired thyroid lobes obtained from intact rats fed a low-I diet. During a 15 min incubation period, concentrations of iodide up to 10-3 M, together with TSH (125 mU/ml), did not affect the thyroid cAMP response to TSH. Preincubation of the lobes in 5 .times. 10-5 M NaI for 2 h preceding a final 15-min incubation in medium containing TSH alone resulted in final cAMP concentrations significantly lower than those in paired lobes not exposed to iodide. Basal cAMP concentrations in thyroids not subjected to TSH stimulation were unaffected by preincubation in iodide. The inclusion of TSH during the preincubation period augmented the inhibitory effect of iodide on the final thyroid cAMP concentration achieved. The inclusion of MMI together with iodide during the preincubation period abolished the inhibitory effect of iodide on the final cAMP concentration achieved by TSH stimulation. Direct measurement of newly formed organic I in vitro demonstrated it was inversely proportional to the final cAMP concentration achieved by TSH stimulation. The preincubation of thyroid lobes in iodide was without effect on the subsequent stimulation of cAMP by PGE1 [prostaglandin E1] or on the stimulation by F- of adenylate cyclase activity in the thyroid homogenate. The data support the concept of an as yet unknown organic form of I that limits thyroid adenylate cyclase responsiveness to TSH stimulation. This may, in part, explain the diverse, and generally inhibitory, actions of iodide on thyroid function.