RETARDED BIOSYNTHESIS OF THYROGLOBULIN SUBUNITS AND THEIR POLYMERIZATION IN VITRO AFTER SUPPRESSION OF TSH SECRETION IN RATS BY CHRONIC ADMINISTRATION OF EXCESS THYROXINE IN THE FORM OF IODINATED CASEIN

Abstract

ABSTRACT The effects of short- and long-term (from 3 days to 28 weeks) administration of excess thyroxine in the form of the iodinated casein "Protamone" (0.2%) to rats on the content of soluble thyroid iodoproteins and on biosynthesis and polymerization of thyroid proteins in vitro were investigated. The concentration of soluble iodoproteins significantly increased (40–80%) up to 2 weeks of treatment, and after that remained at the same level. 27S iodoprotein markedly increased during thyroxine treatment. The content of DNA in the gland and the thyroid weight were a little lower in the treated rats than in the control. The incorporation rate of [14C]leucine into soluble and microsome-bound proteins in vitro was markedly reduced in the treated animals (30–80 % of control). Thyroxine pre-treatment of rats induced retarded synthesis of thyroglobulin and its subunits in vitro. The inhibition of the synthesis of thyroid proteins in vitro and the incrrease in the soluble iodopritein content in the gland in vivo was not correlated with the duration of thyroxine treatment. The immobilization of pre-formed thyroglobulin in the follicle lumen for a long time period is probably an important factor in the enlarged conversion of thyroglobulin into 27S iodoprotein. In conclusion, the long-term suppression of endogenous TSH secretion by administration of thyroxine results in an accumulation of iodoproteins in the thyroid and a reduced rate of synthesis of iodoproteins; after 2 weeks a steady state is reached both with regard to iodoprotein accumulation and synthesis. Finally, the results obtained suggest that the thyroid-pituitary axis becomes adapted to chronic administration of excess thyroxine.