ANTITHYROID ISOFLAVONES FROM SOYBEAN - ISOLATION, CHARACTERIZATION, AND MECHANISMS OF ACTION

The soybean has been implicated in diet-induced goiter by many studies . The extensive consumption of soy products in infant formulas and in Vegetarian diets makes it essential to define the goitrogenic potentia l. In this report, it was observed chat an acidic methanolic extract o f soybeans contains compounds that inhibit thyroid peroxidase- (TPO) c atalyzed reactions essential to thyroid hormone synthesis. Analysis of the soybean extract using HPLC, UV-VIS spectrophotometry, and LC-MS l ed to identification of the isoflavones genistein and daidzein as majo r components by direct comparison with authentic standard reference is oflavones. HPLC fractionation and enzymatic assay of the soybean extra ct showed that the components responsible for inhibition of TPO-cataly zed reactions coeluted with daidzein and genistein. In the presence of iodide ion, genistein and daidzein blocked TPO-catalyzed tyrosine iod ination by acting as alternate substrates, yielding mono-, di-, and tr iiodoisoflavones. Genistein also inhibited thyroxine synthesis using i odinated casein or human goiter thyroglobulin as substrates for the co upling reaction. Incubation of either isoflavone with TPO in the prese nce of H2O2 caused irreversible inactivation of the enzyme; however, t he presence of iodide ion in the incubations completely abolished the inactivation. The IC50 values for inhibition of TPO-catalyzed reaction s by genistein and daidzein were ca. 1-10 mu M, concentrations that ap proach the total isoflavone levels (ca. 1 mu M) previously measured in plasma from humans consuming soy products. Because inhibition of thyr oid hormone synthesis can induce goiter and thyroid neoplasia in roden ts, delineation of anti-thyroid mechanisms for soy isoflavones may be important for extrapolating goitrogenic hazards identified in chronic rodent bioassays to humans consuming soy products. (C) 1997 Elsevier S cience Inc.