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During ovine pregnancy, when both estrogen and progesterone are elevated, prostacyclin (PGI2) production by uterine arteries and the key enzymes for PGI2 production, phospholipase A2 (cPLA2), cyclooxygenase 1 (COX-1), and prostacyclin synthetase (PGIS), are increased. This study was conducted to determine whether exogenous estradiol-17beta (E2beta) with or without progesterone (P4) treatment would increase cPLA2, COX-1, and PGIS protein expression in ovine uterine, mammary, and systemic (renal, mental, and coronary) arteries. Nonpregnant ovariectomized sheep received vehicle (n = 10), P(4) (0.9-g controlled internal drug release vaginal implants; n = 13), E2beta (5 microg/kg bolus followed by 6 microg x kg(-1) x day(-1); n = 10), or P4 + E2beta (n = 12). Arteries were procured on Day 10, and cPLA2, COX-1, and PGIS protein were measured by Western immunoblot analysis in endothelial isolated proteins and vascular smooth muscle (VSM). The levels of cPLA2 was increased in uterine artery endothelium in ewes treated with P4 + E2beta but was not altered by any steroid treatment in renal, coronary, mammary, or omental artery endothelium or in VSM of any evaluated artery. Similarly, COX-1 was increased in uterine artery endothelium with P4 + E2beta but was not significantly altered by treatment in other endothelium or VSM. E2beta treatment increased PGIS protein in uterine and renal artery endothelium but did not alter PGIS in other endothelial tissue. P4 increased PGIS expression in the uterine, mammary, omental, and renal artery VSM, and E2beta increased PGIS expression in the uterine and omental artery VSM. Both E2beta and P4 treatments differentially alter protein expression of the key enzymes involved in PGI2 production in different artery types and may play an important role in the control of blood flow redistribution during hormone replacement therapy.

biology of reproduction

Endothelial Vasodilator Production by Uterine and Systemic Arteries. VIII. Estrogen and Progesterone Effects on cPLA2, COX-1, and PGIS Protein Expression1