Studies on the Mechanism of Action of Liver Extracts in Inhibiting Uptake of131Iin Vitroby the Rat Thyroid Gland

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Abstract
The recently reported in vitro antithyroid action of various rat liver preparations was investigated further with a view to localizing the site of inhibition and ascertaining if liver extracts possessed a similar antithyroid action in vivo. Normal and goitrous rat thyroids were incubated in the presence of various concentrations of liver extract in a medium containing I131. The uptake of I131 by the normal thyroids was greatly depressed by the liver extract, whereas the goitrous thyroids were relatively resistant to this suppressive action. Similar results were obtained with normal thyroids blocked in vitro by 1-methyl-2-mercaptoimidazole (Tapazole). The uptake of I131 by the Tapazole-blocked thyroids was not further inhibited by the antithyroid liver principle. This was explained by the finding that the liver extracts exerted a selective inhibitory action on the formation of organic iodine compounds (determined as trichloro-acetic acid-precipitable I131), in common with the action of propyl-thiouracil or Tapazole. Accordingly, once this process was blocked Tapazole, the liver principle could produce no additional inhibitory effect. Samples of deionlzed liver extract (treated with the anlon exchange resin Bio-Rad AG1-X8 and the cation exchange resin Bio-Rad AG50W-X8) were found to possess undiminished antithyroid activity in vitro. Thyroidal uptake of I131 in vivo was moderately suppressed by iv infusion of extremely large quantities of liver extract. The release of I131 in vivo from prelabeled thyroids was not affected by the liver extract.