Isoflavones regulate secretion of leukemia inhibitory factor and transforming growth factor {beta} and expression of glycodelin in human endometrial epithelial cells.
Isoflavones have attracted much attention due to their association with health benefits; however, comprehensive understanding of the beneficial impacts of isoflavones on uterine biology at the molecular level remains unexplored. In the present study, our data showed that isoflavones aglycones AglyMax, genistein, and equol, but not daidzein, within the range of plasma concentration, displayed bioavailability in regulating the secretion of leukemia inhibitory factor (LIF) and transforming growth factor beta (TGF-beta) in Ishikawa cells, which was blocked by an estrogen receptor antagonist ICI 182 780, mitogen-activated protein kinase kinase (MEK)1/2 inhibitor PD98059, and p38 mitogen-activated protein kinase inhibitor SB203580. We also found that AglyMax and genistein increased in cyclic AMP release and the expression of glycodelin protein in Ishikawa cells assayed using western blot and immunochemical staining. The MEK1/2 inhibitor PD98059 and the protein kinase A inhibitor H89, but not SB203580, attenuated this glycoprotein expression. Moreover, isoflavone aglycones AglyMax stimulated LIF, and TGF-beta secretion, and glycodelin expression in separate primary endometrial epithelial cells in the follicular phase or luteal phase from healthy subject donors. Overall, our findings suggest that isoflavones may alter the uterine expression of estrogen-responsive genes.
Xu
Jin-Wen
JW
Section of Pathophysiology, Department of Pharmacy, School of Pharmacy and Pharmaceutical Sciences, Mukogawa Women's University, Nishinomiya 663-8179, Japan. jwxu@mukogawa-u.ac.jp
Yasui
Naomi
N
Ikeda
Katsumi
K
Pan
Wei-Jun
WJ
Watanabe
June
J
Shiotani
Masahide
M
Yanaihara
Atsushi
A
Miki
Tomohiro
T
Yamori
Yukio
Y
D002478:Cells, Cultured; D000242:Cyclic AMP / Q000502:physiology; D016207:Cytokines / Q000378:metabolism; D004717:Endometrium / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism*; D004847:Epithelial Cells / Q000187:drug effects / Q000378:metabolism; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism; D005260:Female; D000071816:Glycodelin; D006023:Glycoproteins / Q000378:metabolism*; D006801:Humans; D007529:Isoflavones / Q000494:pharmacology*; D053605:Leukemia Inhibitory Factor / Q000378:metabolism*; D011257:Pregnancy Proteins / Q000378:metabolism*; D011960:Receptors, Estrogen / Q000378:metabolism; D016212:Transforming Growth Factor beta / Q000378:metabolism*; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism
D016207:Cytokines; D000071816:Glycodelin; D006023:Glycoproteins; D007529:Isoflavones; C507837:LIF protein, human; D053605:Leukemia Inhibitory Factor; C045246:PAEP protein, human; D011257:Pregnancy Proteins; D011960:Receptors, Estrogen; D016212:Transforming Growth Factor beta; D000242:Cyclic AMP; D048049:Extracellular Signal-Regulated MAP Kinases; D048051:p38 Mitogen-Activated Protein Kinases