Xeno-oestrogens and phyto-oestrogens are alternative ligands for the androgen receptor.
The androgen receptor (AR) plays a critical role in prostate cancer development and progression. This study aimed to use a computerized docking approach to examine the interactions between the human AR and phyto-oestrogens (genistein, daidzein, and flavone) and xeno-oestrogens (bisphenol A, 4-nonylphenol, dichlorodiphenyl trichloroethane [DDT], diethylstilbestrol [DES]). The predicted three-dimensional structure of AR and androgens was established using X-ray diffraction. The binding of four xeno-oestrogens and three phyto-oestrogens to AR was analysed. The steroids estradiol and dihydrotestosterone (DHT) were used as positive controls and thyroxine as negative control. All the ligands shared the same binding site except for thyroxine. The endogenous hormones DHT and 17beta-oestradiol showed the strongest binding with the lowest affinity energy (< -10 kcal mol(-1)). All three phyto-oestrogens and two xeno-oestrogens (bisphenol A and DES) showed strong binding to AR. The affinities of flavone, genistein, and daidzein were between -8.8 and -8.5 kcal mol(-1), while that of bisphenol A was -8.1 kcal mol(-1) and DES -8.3 kcal mol(-1). Another two xeno-oestrogens, 4-nonylphenol and DDT, although they fit within the binding domain of AR, showed weak affinity (-6.4 and -6.7 kcal mol(-1), respectively). The phyto-oestrogens genistein, daidzein and flavone, and the xeno-oestrogens bisphenol A and DES can be regarded as androgenic effectors. The xeno-oestrogens DDT and 4-nonylphenol bind only weakly to AR.
Wang
Hao
H
School of Life Sciences, Northeast Normal University, Changchun, China.
Li
Jiang
J
Gao
Yang
Y
Xu
Ying
Y
Pan
Ying
Y
Tsuji
Ichiro
I
Sun
Zi-Jie
ZJ
Li
Xiao-Meng
XM
D001559:Benzhydryl Compounds; D003198:Computer Simulation; D003634:DDT / Q000378:metabolism; D004054:Diethylstilbestrol / Q000378:metabolism; D047309:Flavones / Q000378:metabolism; D019833:Genistein / Q000378:metabolism; D006801:Humans; D007529:Isoflavones / Q000378:metabolism; D008024:Ligands; D010636:Phenols / Q000378:metabolism; D048789:Phytoestrogens / Q000378:metabolism*; D011944:Receptors, Androgen / Q000378:metabolism*; D000098826:Bisphenol A Compounds
D001559:Benzhydryl Compounds; D003634:DDT; D004054:Diethylstilbestrol; D047309:Flavones; D019833:Genistein; D007529:Isoflavones; D008024:Ligands; D010636:Phenols; D048789:Phytoestrogens; D011944:Receptors, Androgen; C004742:daidzein; C041594:4-nonylphenol; C006780:bisphenol A; D000098826:Bisphenol A Compounds; C043562:flavone