Mechanisms of 17beta-estradiol on the production of ET-1 in ovariectomized rats.
In order to clarify the mechanism underlying the possible preventive effect of estrogen on atherogenesis, we investigated the role of 17beta-estradiol (E2) in the regulation of endothelin-1 (ET-1) production in ovariectomized rats, which may contribute to atherogenesis. Female Spragure-Dawly rats were randomly divided into three groups: sham-operated group (sham), ovariectomized group (OVX) and 17beta-estradiol replacement group (OVX + E2, 20 microg(-1).kg.d(-1),s.c.). 4 weeks after operation, the plasma concentration of ET-1, clearance of ET-1, functional ECE activity and preproET-1 mRNA expression in aorta were measured. Concentration of plasma ET-1 change from 107.8 +/- 18.3 pg/ml (sham) and 135.5 +/- 27.6 pg/ml (OVX + E2) to 190.7 +/- 25.5 pg/ml (OVX ) (n = 8, p < 0.05). There was no significant difference in the clearance of 125IET-1 among three groups (p > 0.05). Functional ECE activity was increased in OVX group in comparison to that in sham group (p < 0.05). The OVX increased the preproET-1 mRNA expression in sham, whereas treatment with estrogen reversed these changes (p < 0.05). The present study have shown that estrogen down-regulates plasma ET-1 levels by inhibiting the preproET-1 mRNA expression and functional ECE activity. Clearance of ET-1 was not affected. Inhibition of ET-1 production mediated by modulating ECE activity may be one of the novel mechanisms of the protective of estrogens on the cardiovascular system.
D000818:Animals; D001013:Aorta, Thoracic / Q000187:drug effects* / Q000378:metabolism; D016282:Aspartic Acid Endopeptidases / Q000097:blood; D019332:Endothelin-1 / Q000097:blood* / Q000235:genetics; D000072396:Endothelin-Converting Enzymes; D004958:Estradiol / Q000008:administration & dosage / Q000494:pharmacology*; D005260:Female; D066298:In Vitro Techniques; D007279:Injections, Subcutaneous; D008666:Metalloendopeptidases; D009119:Muscle Contraction / Q000187:drug effects; D009131:Muscle, Smooth, Vascular / Q000187:drug effects / Q000378:metabolism; D010052:Ovariectomy; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D020133:Reverse Transcriptase Polymerase Chain Reaction
D019332:Endothelin-1; D012333:RNA, Messenger; D004958:Estradiol; D016282:Aspartic Acid Endopeptidases; D008666:Metalloendopeptidases; D000072396:Endothelin-Converting Enzymes