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1 February 2002 Endothelial Vasodilator Production by Uterine and Systemic Arteries. VIII. Estrogen and Progesterone Effects on cPLA2, COX-1, and PGIS Protein Expression
Heidi L. Rupnow, Terrance M. Phernetton, Mary L. Modrick, Milo C. Wiltbank, Ian M. Bird, Ronald R. Magness
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Abstract

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-17β (E2β) 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), P4 (0.9-g controlled internal drug release vaginal implants; n = 13), E2β (5 μg/kg bolus followed by 6 μg kg−1 day−1; n = 10), or P4 E2β (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 E2β 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 E2β but was not significantly altered by treatment in other endothelium or VSM. E2β 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 E2β increased PGIS expression in the uterine and omental artery VSM. Both E2β 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.

Heidi L. Rupnow, Terrance M. Phernetton, Mary L. Modrick, Milo C. Wiltbank, Ian M. Bird, and Ronald R. Magness "Endothelial Vasodilator Production by Uterine and Systemic Arteries. VIII. Estrogen and Progesterone Effects on cPLA2, COX-1, and PGIS Protein Expression," Biology of Reproduction 66(2), 468-474, (1 February 2002). https://doi.org/10.1095/biolreprod66.2.468
Published: 1 February 2002
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