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Mäkelä S, Poutanen M, Lehtimäki J, Kostian ML, Santti R,
Vihko R. Proc Soc Exp Biol Med 1995 Jan 208:1 51-9.
Abstract
Several plant estrogens, especially coumestrol and genistein,
were found to reduce the conversion of [3H]estrone to [3H] 17 beta-estradiol
catalyzed by estrogen-specific 17 beta-hydroxysteroid oxidoreductase
Type 1 (E.C. 1.1.1.62) in vitro. Coumestrol, the most potent inhibitor
in our experiments, is the best inhibitor of the enzyme known to
date. All compounds with inhibitory effects were also estrogenic.
However, structural demands for 17 beta-HSOR Type 1 inhibition and
estrogenicity of tested compounds in breast cancer cells (judged
by increased cell proliferation) were not identical. Zearalenone
and diethylstilbestrol, both potent estrogens, did not inhibit 17
beta-HSOR Type 1. Thus, changes in the estrogen molecule may discriminate
between active sites of 17 beta-HSOR Type 1 and estrogen binding
sites of the ER. The effects of these compounds in vivo cannot be
predicted on the basis of these results. Inhibition of 17 beta-HSOR
Type 1 enzyme could lead to a decrease in the availability of the
highly active endogenous estrogen. However, these compounds are
estrogenic per se, and they may thus replace endogenous estrogens.
Additional studies are needed to further understand the role of
these plant estrogens in the etiology of hormone-dependent cancers.
It is not easily conceivable how the chemopreventive action of Asian
diets, possibly mediated by phytoestrogens in soya products, can
be based on the inhibition of estrone reduction at the target cells
by phytoestrogens or related compounds, unless they are ''incomplete
estrogens'' (i.e., unable to induce all effects typical of endogenous
estrogens).
Author Address
Institute of Biomedicine, University of Turku, Finland.
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