PARENT SESSION
Uterus/Oviduct

ENDOTHELIAL VASODILATOR PRODUCTION BY UTERINE AND SYSTEMIC ARTERIES: ESTROGEN AND PROGESTERONE EFFECTS ON CPLA2, COX-1, AND PGIS PROTEIN EXPRESSION.

Rupnow, Heidi¹, Phernetton, Terrance¹, Modrick, Mary ¹, Wiltbank, Milo², Bird, Ian ¹, Magness, Ronald^1,3, ^{1 2 3}

ABSTRACT- During ovine pregnancy, when both estrogen and progesterone are elevated, PGI2 production by uterine arteries and the key enzymes for PGI2 production, cPLA2, COX-1, and PGIS, are increased. Purpose: To determine if exogenous Estradiol-17 (E2B) ±progesterone (P4) would increase cPLA2, COX-1, and PGIS protein expression in ovine uterine, mammary, and systemic (renal, omental, and coronary) arteries. Methods: Nonpregnant ovariectomized sheep received either Vehicle (V; n=10), P4 (0.9g CIDRs vaginal implants; n=13), E2B(5g/kg bolus followed by 6g/kg/d; n=10), or P4 + E2B(n=12). Arteries were procured on day 10 and cPLA2, COX-1, and PGIS protein was measured by Western immunoblot analysis in endothelial isolated proteins and VSM. Results: cPLA2 was increased in uterine artery endothelium in P4 + E2B treated ewes, but was unaltered by treatment in renal and coronary artery endothelium and VSM of the uterine artery. Furthermore, cPLA2 was below detectable amounts in mammary and omental artery endothelium as well as mammary, omental, renal, and coronary VSM. COX-1 was increased with P4 + E2B treatment in uterine artery endothelium, unaltered with steroid treatment in mammary, renal, omental, and coronary artery endothelium and was not detectable in VSM of any artery type. PGIS was increased in uterine artery endothelium with E2B and unaltered in coronary, renal, and omental artery endothelium. P4 increased PGIS expression in the uterine, mammary, omental, and renal artery VSM, while E2B and P4 + E2B increased PGIS expression in the uterine and omental artery VSM. Conclusions: Both E2B and P4 treatments differentially alter protein expression key enzymes in PGI2 production in different artery types and may play a role in the control of blood flow redistribution during hormone replacement therapy. Support: NIH HL49210, HL56702, HD33255, HD38843.

KEY WORDS: uterine artery, prostacyclin