|
|
- Dietary estrogenic isoflavones are potent inhibitors
of beta-hydroxysteroid dehydrogenase of P. testosteronii.
- Keung WM. Biochem Biophys Res Commun 1995 Oct 24 215:3 1137-44
- Abstract
- The isoflavones daidzein, genistein, biochanin A and formononetin
selectively inhibit the gamma-isozymes of mammalian alcohol dehydrogenase
(ADH). Since gamma-ADH is the only ADH isoform that catalyzes
3 beta-hydroxysteroid oxidation, it was conjectured that these
isoflavones might also inhibit other enzymes involved in 3 beta-hydroxysteroid
metabolism. P. testosteronii beta-hydroxysteroid dehydrogenase
(beta-HSD) was used to evaluate this hypothesis. Indeed, all isoflavones
that inhibit gamma-ADH were found to be potent inhibitors of beta-HSD.
Both the 3 beta- and 17 beta-HSD activities of the enzyme are
inhibited. Kinetic analyses with pregnenolone (3-beta-OH) and
testosterone (17-beta-OH) as substrates reveal that daidzein and
genistein inhibit beta-HSD competitively with respect to the sterol
substrates. Their Ki values are very similar and range from 0.013
to 0.02 microM. These results suggest that isoflavones may exert
some of their biological effects by modulating activities of enzymes
that metabolize steroids critical to hormonal and/or neuronal
functions.
-
- Estrogen-specific 17 beta-hydroxysteroid oxidoreductase
type 1 (E.C. 1.1.1.62) as a possible target for the action of
phytoestrogens.
- 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).
|
