The role of peroxisome proliferator-activated receptor-gamma and estrogen receptors in genistein-induced regulation of vascular tone in female rat aortas.
BACKGROUND
Genistein (GST) is a phytoestrogen that binds estrogen receptors (ER) to produce a protective cardiovascular effect. It also has been shown binding peroxisome proliferator-activated receptor-gamma (PPAR-gamma).


METHODS
In the present study, we assessed the role of PPAR-gamma and ER in GST-mediated regulation of vascular tone in female rat aortas by in vitro tension measurement, immunohistochemistry, immunofluorescence, immunoprecipitation and Western blot analysis.


RESULTS
In aortas pretreated with GW9662 (inhibitor of PPAR-gamma), ICI182780 (inhibitor of ER) and a combination of GW9662 and ICI182780, the magnitudes of GST-induced dilatation were attenuated. N(G)-nitro-L-arginine methyl ester had a similar effect. ER-beta and PPAR-gamma colocalized in all 3 layers of the aortas, while ER-alpha and PPAR-gamma colocalized only in the vascular endothelium and adventitia. In GST-treated whole-cell protein samples, we demonstrated coimmunoprecipitation of ER-beta (not ER-alpha) and PPAR-gamma. The expression of ER-beta and PPAR-gamma in nuclear protein from GST-treated samples increased, which was partially reversed by either GW9662 or ICI182780 and more efficiently reversed using a combination of GW9662 and ICI182780.


CONCLUSIONS
Our findings suggest that GST can relax phenylephrine-induced vascular contraction in female rat aortas, which is mediated by PPAR-gamma and ER-beta.
Xiang
Qiuling
Q
Department of Physiology, Zhongshan School of Medicine, Sun Yat-Sen University, Guangzhou, China.
Lin
Guiping
G
Fu
Xiaodong
X
Wang
Shuzhen
S
Wang
Tinghuai
T
D000818:Animals; D001013:Aorta, Thoracic / Q000166:cytology / Q000187:drug effects*; D002467:Cell Nucleus / Q000187:drug effects / Q000378:metabolism; D047628:Estrogen Receptor alpha / Q000037:antagonists & inhibitors / Q000502:physiology*; D047629:Estrogen Receptor beta / Q000037:antagonists & inhibitors / Q000502:physiology; D005260:Female; D019833:Genistein / Q000494:pharmacology*; D007150:Immunohistochemistry; D047468:Immunoprecipitation; D066298:In Vitro Techniques; D009569:Nitric Oxide / Q000037:antagonists & inhibitors; D009928:Organ Specificity; D047495:PPAR gamma / Q000037:antagonists & inhibitors / Q000502:physiology*; D048789:Phytoestrogens / Q000494:pharmacology*; D021381:Protein Transport / Q000187:drug effects; D051381:Rats; D017207:Rats, Sprague-Dawley; D014664:Vasodilation / Q000187:drug effects*; D014665:Vasodilator Agents / Q000494:pharmacology*
D047628:Estrogen Receptor alpha; D047629:Estrogen Receptor beta; D047495:PPAR gamma; D048789:Phytoestrogens; D014665:Vasodilator Agents; D009569:Nitric Oxide; D019833:Genistein