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Pharmacological Reviews, Vol 15, 43-95, Copyright © 1963 by the American Society for Pharmacology and Experimental Therapeutics

INTERMEDIARY METABOLISM OF THYROID TISSUE AND THE ACTION OF DRUGS

FARAHE MALOOF 1 and MORRIS SOODAK 1

1 Graduate Department of Biochemistry, Brandeis University, Waltham, Massachusetts, and Department of Medicine, Harvard Medical School and the Medical Service of the Massachusetts General Hospital, Boston, Massachusetts

It is clear from this review that some progress has been made in defining thyroid function at a basic level. A stumbling block to the precise localization of various mechanisms is the anatomical structure of the thyroid, i.e., a division into two major components—foilicular cells and follicular colloid. Detailed observations of isolated functional follicular cells should help solve this dilemma. Nevertheless, it appears likely that the follicular cell with its complement of cytostructural components is the initiating locus of the important reactions in the thyroid.

Progress has been made regarding carbohydrate and lipid metabolism in thyroid tissue. Further studies along these lines should be forthcoming and will be invaluable in defining the energetics of thyroid tissue. Similar progress in protein synthesis, in particular, thyroglobulin synthesis, is lacking.

New and systematic methods of study are contributing greatly to the evaluation of the iodide-concentrating mechanism. A maze of data concerning the iodination reaction has been published and it is difficult to evaluate them critically because of the wide variety of techniques and systems employed by various investigators. Although the weight of evidence suggests that a peroxidase is involved in the iodinating system, the precise role of the peroxidase remains to be elucidated. It will be important to acquire knowledge concerning the endogenous hydrogen peroxide-generating system within the thyroid. Furthermore, the actual concentration of peroxide as well as the factors which control its level must be determined. The nature of the iodinating intermediate remains an enigma, but on the basis of preliminary studies, a sulfenyl iodide (RSI) suggests itself as a likely possibility.

This review of antithyroid drugs has been largely limited to specific compounds, the metabolic pathways of which have been studied. This obviously has limited the report. Observations involving the thiocarbamides continue to play a crucial part in evaluating thyroid function. Recent studies with the thiocarbamides, thiourea in particular, have been informative and have led to a new concept in thyroid physiology, i.e., the possible role of a disulfide bond in thyroid tissue, not only as a locus for the inhibitory action of these compounds but as an initiating site for the iodination reaction.

Note:

The authors are grateful to Dr. W. Bauer and Dr. E. B. Astwood for a careful and critical review of the manuscript, to Dr. Leonard Spector for helpful discussions, to Miss Genevieve Cole for aid in compiling and reviewing the bibliography, and to Miss Ngoc-Anh Nguyen and Mr. Henry Guerin for technical assistance.




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