Genistein supplementation stimulates the oxytocin system in the aorta of ovariectomized rats.
OBJECTIVE
In the present study, we localized oxytocin (OT) and its receptor (OTR) in the rat aorta, and investigated whether genistein, an isoflavonic phytoestrogen, influences their expression in ovariectomized (OVX) rats deficient in estrogen.


RESULTS
OVX Sprague-Dawley rats were randomized to the following groups: genistein (from 0.02 to 5 microg/g/day, s.c. for 10 days), estradiol (E(2,) 0.1 microg/g/day, s.c. for 10 days) or their respective vehicles. OT and OTR immunostaining was concentrated in the aortic tunica intima, suggesting their paracrine/autocrine action within endothelial cells. Reverse transcription-polymerase chain reaction analysis showed that 1 and 5 microg/g but not 0.1 microg/g genistein elevated OT mRNA (2-fold P<0.05), OTR mRNA (2.5-fold, P<0.05) and endothelial nitric oxide synthase (eNOS) mRNA (2-fold, P<0.05) in the aorta of OVX rats. In addition, genistein treatment increased estrogen receptor alpha (ERalpha) (2- to 3-fold, P<0.05) but resulted in a 50% decrease of ERbeta (P<0.05). These genistein effects were neutralized by treatment of OVX rats with the ER antagonist ICI 182,780 (1.5 microg/g/day, s.c. for 10 days). Similarly, Western blot analysis revealed an increase of 67-kDa OTR, 140-kDa eNOS, 62-kDa ERalpha and a decrease of 55-kDa ERbeta (P<0.05) in the aorta of OVX rats treated with genistein. In contrast, the treatment of OVX rats with E(2) elevated ERbeta mRNA (1.5 fold, P<0.05) but similarly to genistein increased OT, OTR, eNOS and ERalpha mRNA.


CONCLUSIONS
These results provide the first evidence of OT and OTR co-localization in endothelial cells. The response to genistein via ER activation can be regarded as a recovery from endothelial dysfunction induced by ovariectomy.
Wang
Donghao
D
Laboratory of Cardiovascular Biochemistry, Centre Hospitalier de l'Université de Montréal--Hôtel-Dieu, 3850 St. Urbain Street, Masson Pavilion, Montreal, Quebec, Canada H2W 1T7.
Gutkowska
Jolanta
J
Marcinkiewicz
Mieczyslaw
M
Rachelska
Grazyna
G
Jankowski
Marek
M
D000818:Animals; D001011:Aorta; D001835:Body Weight / Q000187:drug effects; D047628:Estrogen Receptor alpha; D047629:Estrogen Receptor beta; D005260:Female; D019833:Genistein / Q000494:pharmacology*; D006131:Growth Inhibitors / Q000494:pharmacology*; D007150:Immunohistochemistry; D019001:Nitric Oxide Synthase / Q000032:analysis / Q000235:genetics / Q000378:metabolism; D052250:Nitric Oxide Synthase Type III; D009929:Organ Size / Q000187:drug effects; D010052:Ovariectomy; D010121:Oxytocin / Q000235:genetics / Q000378:metabolism*; D012333:RNA, Messenger / Q000032:analysis; D051381:Rats; D017207:Rats, Sprague-Dawley; D011960:Receptors, Estrogen / Q000032:analysis / Q000235:genetics; D018045:Receptors, Oxytocin / Q000235:genetics / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013268:Stimulation, Chemical; D017539:Tunica Intima / Q000378:metabolism*; D014599:Uterus / Q000033:anatomy & histology
D047628:Estrogen Receptor alpha; D047629:Estrogen Receptor beta; D006131:Growth Inhibitors; D012333:RNA, Messenger; D011960:Receptors, Estrogen; D018045:Receptors, Oxytocin; D010121:Oxytocin; D019833:Genistein; D019001:Nitric Oxide Synthase; D052250:Nitric Oxide Synthase Type III; C496316:Nos3 protein, rat