Harris R M, Wood D M, Bottomley L, Blagg S, Owen K, Hughes P J, Waring R H, Kirk C J
School of Biosciences and Medical School, University of Birmingham, Edgbaston, Birmingham B15 2TT, United Kingdom.
J Clin Endocrinol Metab. 2004 Apr;89(4):1779-87. doi: 10.1210/jc.2003-031631.
We investigated the ability of 37 flavonoids and flavonoid sulfoconjugates, including some abundant dietary constituents, to act as substrates and/or inhibitors of the sulfotransferase and sulfatase enzymes that interconvert active estrogens and inactive estrogen sulfates in human tissues. The enzymes studied include estrogen sulfotransferase, the thermostable phenolsulfotransferase that acts on a range of substrates including estrogens; steroid sulfatase; and two related enzymes, monoamine phenolsulfotransferase and arylsulfatase A. Several dietary flavonoids, including the soy isoflavones genistein and daidzein, were sulfated by these human sulfotransferases. Many flavonoids were potent inhibitors of thermostable phenolsulfotransferase. Genistein and equol were potent mixed inhibitors of hepatic estrogen sulfotransferase, with inhibitory constant values of 500 nM and 400 nM, respectively. Monoamine phenolsulfotransferase activity was relatively unaffected by flavonoids, but this enzyme was mainly responsible for the sulfation of flavonoids at concentrations greater than 1 micro M. Of the compounds tested, only daidzein 4,7-bisulfate, a trace metabolite in humans, significantly inhibited steroid sulfatase in the micromolar concentration range. Hence, dietary flavonoids may be able to influence the bioavailability of endogenous estrogens, and disrupt endocrine balance, by increasing the ratio of active estrogens to inactive estrogen sulfates in human tissues.
我们研究了37种黄酮类化合物及黄酮类硫酸共轭物（包括一些常见的膳食成分）作为磺基转移酶和硫酸酯酶的底物及/或抑制剂的能力，这些酶在人体组织中可使活性雌激素与无活性雌激素硫酸盐相互转化。所研究的酶包括雌激素磺基转移酶、作用于包括雌激素在内多种底物的耐热性酚磺基转移酶、类固醇硫酸酯酶，以及两种相关酶，即单胺酚磺基转移酶和芳基硫酸酯酶A。几种膳食黄酮类化合物，包括大豆异黄酮染料木黄酮和黄豆苷元，可被这些人体磺基转移酶硫酸化。许多黄酮类化合物是耐热性酚磺基转移酶的强效抑制剂。染料木黄酮和雌马酚是肝脏雌激素磺基转移酶的强效混合型抑制剂，抑制常数分别为500 nM和400 nM。黄酮类化合物对单胺酚磺基转移酶活性影响相对较小，但在浓度大于1微摩尔时，该酶主要负责黄酮类化合物的硫酸化。在所测试的化合物中，只有黄豆苷元4,7 - 二硫酸酯（一种人体微量代谢物）在微摩尔浓度范围内能显著抑制类固醇硫酸酯酶。因此，膳食黄酮类化合物可能通过提高人体组织中活性雌激素与无活性雌激素硫酸盐的比例，影响内源性雌激素的生物利用度，并扰乱内分泌平衡。
