BIPHASIC EFFECT OF TSH ON THYROIDAL IODIDE COLLECTION IN RATS12

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Abstract
Assessing the activity of the thyroidal iodide pump by measuring the thyroid/serum radioiodide gradient (T/S), we found the stimulatory effect of TSH to have a latency of from about 8 hours to 12 hours or more. The longer latent periods were observed in rats whose initial T/S was relatively high. The rise in the T/S was preceded by a depression of this ratio, whether hypophysectomized, normal, or triiodothyronine (T3) treated rats were injected with TSH. This biphasic response was elicited with Armour TSH, lyophilized rat pituitary tissue and Bates'' highly purified mouse tumor and bovine TSH preparations; it seems therefore reasonable to attribute it to TSH proper rather than some contaminant(s). The same kind of response was also observed in rats whose thyroids were purged of organic iodine with goitrogens and whose endogenous TSH output was subsequently inhibited by giving T3 along with the antithyroid drugs; this indicates that the initial depression of the T/S is not due to flooding of the thyroidal iodide pool with stable iodide derived from iodotyrosines through deiodination, nor to inhibition of iodide pump activity by iodothyronines liberated from thyroglobulin by TSH. When organic binding of iodine was not blocked, stimulation of thyroidal I131 uptake was observed in hypophysectomized rats 4 hours after the injection of TSH, although in blocked glands of similar animals the T/S was depressed. Unidirectional active iodide clearance by the thyroid (estimated on the basis of clearance during the first 3 minutes following injection of I131) was unchanged in hypophysectomized rats examined 4 hours after the injection of TSH, but the thyroids of such rats lost in vivo accumulated radioiodide at a faster rate in vitro than did those of untreated hypophysectomized animals. It therefore appears that a relatively early effect of TSH may be an enhancement of the exit rate constant for thyroidal iodide (increased permeability of thyroid cell membranes?). The stimulating influence of TSH on the active uptake of iodide by the rat thyroid, on the other hand, is remarkably slow. Differences between the periods of latency for the effects of TSH on various thyroid functions are discussed.