Endothelial vasodilator production by uterine and systemic arteries. VII. Estrogen and progesterone effects on eNOS.
Uterine blood flow (UBF) and uterine artery endothelial nitric oxide synthase (eNOS) expression are greatest during the follicular vs. luteal phase. 17 beta-Estradiol (E(2)beta) increases UBF and elevates eNOS in ovine uterine but not systemic arteries; progesterone (P(4)) effects on E(2)beta changes of eNOS remain unclear. Nonpregnant ovariectomized sheep received either vehicle (n = 10), P(4) (0.9 g Controlled Internal Drug Release vaginal implants; n = 13), E(2)beta (5 microg/kg bolus + 6 microg x kg(-1) x day(-1); n = 10), or P(4) + E(2)beta (n = 12). Reproductive (uterine/mammary) and nonreproductive (omental/renal) artery endothelial proteins were procured on day 10, and eNOS was measured by Western analysis. P(4) and E(2)beta alone and in combination increased (P < 0.05) eNOS expression in uterine artery endothelium (vehicle = 100 +/- 16%, P(4) = 251 +/- 59%, E(2)beta = 566 +/- 147%, P(4) + E(2)beta = 772 +/- 211% of vehicle). Neither omental, renal, nor mammary artery eNOS was altered, demonstrating the local nature of steroid-induced maintenance of uterine arterial eNOS. In the myometrial microvasculature, eNOS was increased slightly (P = 0.06) with E(2)beta and significantly with P(4) + E(2)beta. Systemic NO(x) was increased with P(4) and P(4) + E(2)beta, but not E(2)beta, suggesting differential regulation of eNOS expression and activity, since P(4) increased eNOS in uterine artery endothelium while E(2)beta and the combination further increased eNOS protein.
Department of Obstetrics and Gynecology, Perinatal Research Laboratories, University of Wisconsin-Madison, Madison, Wisconsin 53715, USA.
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Rupnow
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Phernetton
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Modrick
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Bird
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D000818:Animals; D001158:Arteries / Q000502:physiology*; D004730:Endothelium, Vascular / Q000502:physiology*; D004967:Estrogens / Q000494:pharmacology*; D005260:Female; D015971:Gene Expression Regulation, Enzymologic / Q000187:drug effects / Q000502:physiology*; D008321:Mammary Glands, Animal / Q000098:blood supply; D008833:Microcirculation / Q000502:physiology; D009131:Muscle, Smooth, Vascular / Q000502:physiology*; D009215:Myometrium / Q000098:blood supply*; D019001:Nitric Oxide Synthase / Q000235:genetics*; D052250:Nitric Oxide Synthase Type III; D009589:Nitrogen Oxides / Q000378:metabolism; D009852:Omentum / Q000098:blood supply; D010052:Ovariectomy; D011374:Progesterone / Q000494:pharmacology*; D012077:Renal Artery / Q000502:physiology; D012756:Sheep; D014599:Uterus / Q000098:blood supply*; D014664:Vasodilation / Q000502:physiology
D004967:Estrogens; D009589:Nitrogen Oxides; D011374:Progesterone; D019001:Nitric Oxide Synthase; D052250:Nitric Oxide Synthase Type III