Novel action of estrone on vascular tissue: regulation of NOS and COX activity.
The hypothesis tested in the present work is that estrone non-genomically regulates aortic nitric oxide synthase (NOS) and cyclooxygenase (COX) activities in female rats, and that such regulation depends on ovarian function. We found that physiological concentrations of estrone (E(1)) (0.1-10nM) significantly increased nitric oxide (NO) production (133 and 163% above control). The stimulatory action of E(1) on NOS activity was independent of calcium influx since the increase in NO elicited by the hormone was not affected by EGTA or verapamil. When COX activity was measured, we observed that estrone enhanced thromboxane (TXB(2)) production and prostacyclin (PGI(2)) release, but not prostaglandin (PGF(2), PGD(2), and PGE(2)) synthesis. Finally we demonstrated that the hormonal effect on NOS activity was not detected in rat aortic strips (RAS) isolated from animals deprived of ovarian activity (FR(-)) or ovariectomized rats (OVX). These results suggest that estrone exerts a direct, non-genomic action on rat aortic metabolism, which involves NOS and COX activation and depends on ovarian activity.
Selles
Juana
J
Cátedra de Analisis Clínicos II, Departamento de Biología, Bioquímica y Farmacia, Universidad Nacional del Sur, San Juan 670, B8000ICN Bahia Blanca, Argentina.
Polini
Nélida
N
Alvarez
Cristina
C
Massheimer
Virginia
V
D000818:Animals; D001011:Aorta / Q000187:drug effects* / Q000201:enzymology; D004305:Dose-Response Relationship, Drug; D015777:Eicosanoids / Q000032:analysis / Q000096:biosynthesis; D004970:Estrone / Q000494:pharmacology*; D005260:Female; D015971:Gene Expression Regulation, Enzymologic / Q000187:drug effects*; D019001:Nitric Oxide Synthase / Q000235:genetics / Q000378:metabolism*; D010052:Ovariectomy; D011451:Prostaglandin-Endoperoxide Synthases / Q000235:genetics / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar
D015777:Eicosanoids; D004970:Estrone; D019001:Nitric Oxide Synthase; D011451:Prostaglandin-Endoperoxide Synthases