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- Divi RL, Chang HC, Doerge DR.
- Biochem Pharmacol 1997 Nov 15 54:10 1087-96.
- Abstract
- 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
potential. In this report, it was observed that an acidic methanolic
extract of soybeans contains compounds that inhibit thyroid peroxidase-
(TPO) catalyzed reactions essential to thyroid hormone synthesis.
Analysis of the soybean extract using HPLC, UV-VIS spectrophotometry,
and LC-MS led to identification of the isoflavones genistein and
daidzein as major components by direct comparison with authentic
standard reference isoflavones. HPLC fractionation and enzymatic
assay of the soybean extract showed that the components responsible
for inhibition of TPO-catalyzed reactions coeluted with daidzein
and genistein. In the presence of iodide ion, genistein and daidzein
blocked TPO-catalyzed tyrosine iodination by acting as alternate
substrates, yielding mono-, di-, and triiodoisoflavones. Genistein
also inhibited thyroxine synthesis using iodinated casein or human
goiter thyroglobulin as substrates for the coupling reaction.
Incubation of either isoflavone with TPO in the presence of H2O2
caused irreversible inactivation of the enzyme; however, the presence
of iodide ion in the incubations completely abolished the inactivation.
The IC50 values for inhibition of TPO-catalyzed reactions by genistein
and daidzein were ca. 1-10 microM, concentrations that approach
the total isoflavone levels (ca. 1 microM) previously measured
in plasma from humans consuming soy products. Because inhibition
of thyroid hormone synthesis can induce goiter and thyroid neoplasia
in rodents, 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.
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- Author Address
- National Center for Toxicological Research, Jefferson, AR 72079,
USA.
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