Anti-thyroid isoflavones from soybean: isolation,
characterization, and mechanisms of action
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.
Author Address
National Center for Toxicological Research, Jefferson, AR 72079,
USA.
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