Actions of the soy phytoestrogen genistein in models of human chronic disease: potential involvement of transforming growth factor beta.
The structural similarity, but non-identity, between 17beta-oestradiol and the soy phytoestrogen genistein suggests that the two compounds will have actions that may be identical in some target biological systems, but different in others. Epidermal growth factor (EGF)-stimulated proliferation of human mammary epithelial cells (that do not express the oestrogen receptor) was significantly suppressed at genistein concentrations (5-10 microM) that are attainable physiologically. Others have shown previously that transforming growth factor beta (TGFbeta) has similar growth-inhibitory effects on human cells. Analysis of the conditioned medium of human mammary epithelial cells exposed to genistein plus EGF showed increased levels of TGFbeta relative to those in the medium of cells exposed to EGF or genistein alone. Related experiments in a primate model of menopause demonstrated that ingestion of soy containing isoflavones was correlated with the suppression of neurodegeneration-relevant phosphorylation of the microtubule-associated protein tau, while intake of Premarin (a hormone replacement therapy that is commonly prescribed for women) was not correlated. The results discussed here indicate that genistein, and probably other related phytoestrogens, have pleiotropic actions, some of which may involve TGFbeta activity.
Kim
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H
Department of Pharmacology and Toxicology, University of Alabama at Birmingham, 1670 University Boulevard, Birmingham, AL 35294-0019, U.S.A. helenkim@uab.edu
Xu
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J
Su
Y
Y
Xia
H
H
Li
L
L
Peterson
G
G
Murphy-Ullrich
J
J
Barnes
S
S
D000818:Animals; D001921:Brain / Q000187:drug effects / Q000378:metabolism; D002460:Cell Line; D002908:Chronic Disease; D002986:Clinical Trials as Topic; D017077:Culture Media, Conditioned / Q000378:metabolism; D015914:Estrogen Replacement Therapy; D004966:Estrogens, Conjugated (USP) / Q000737:chemistry / Q000494:pharmacology; D005260:Female; D019833:Genistein / Q000737:chemistry / Q000494:pharmacology*; D006801:Humans; D008252:Macaca fascicularis; D010766:Phosphorylation / Q000187:drug effects; D017698:Postmenopause / Q000187:drug effects; D011960:Receptors, Estrogen / Q000378:metabolism; D015398:Signal Transduction; D013025:Glycine max; D016212:Transforming Growth Factor beta / Q000378:metabolism*; D014443:Tyrosine / Q000737:chemistry; D016875:tau Proteins / Q000378:metabolism
D017077:Culture Media, Conditioned; D004966:Estrogens, Conjugated (USP); D011960:Receptors, Estrogen; D016212:Transforming Growth Factor beta; D016875:tau Proteins; D014443:Tyrosine; D019833:Genistein