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Regulation of Prostaglandin Endoperoxide H Synthase 1 and 2 by Estradiol and Progesterone in Nonpregnant Ovine Myometrium and Endometrium in Vivo¹

Laboratory of Pregnancy and Newborn Research, Physiology Department, Cornell University College of Veterinary Medicine, Ithaca, New York 14853

Address all correspondence and requests for reprints to: Peter W. Nathanielsz, M.D., Ph.D., Sc.D., Laboratory for Pregnancy and Newborn Research, Department of Physiology, T9 016 VRT, Cornell University College of Veterinary Medicine, Ithaca, New York 14853-6401. E-mail: pwn1{at}cornell.edu

PG endoperoxide H synthase-2 (PGHS-2) messenger RNA (mRNA) and protein levels are increased dramatically in ovine myometrium and endometrium during both glucocorticoid-induced premature labor and spontaneous term labor. In this study, we examined estradiol and progesterone regulation in vivo of PGHS-1 and PGHS-2 expression at both mRNA and protein levels using a nonpregnant ovariectomized sheep model. We determined the differential distribution of PGHS-2 and PGHS-1 in ovine myometrium and endometrium with immunocytochemistry. Twenty ovariectomized ewes were treated with saline (n = 5) or estradiol infused iv for 2 days (50 µg/day; n = 5) or an intravaginal progesterone sponge for 10 days (containing 0.3 g progesterone; n = 5) or an intravaginal progesterone sponge for 10 days with estradiol (50 µg/day) administered on days 9 and 10 with the progesterone sponge still in place (EP; n = 5). PGHS-1 and -2 mRNA and protein were measured by Northern and Western blot analyses, respectively. PGHS-2 mRNA and protein abundance increased significantly in myometrium after estradiol treatment (P < 0.01). In contrast, progesterone was a more potent stimulator than estradiol of PGHS-2 protein abundance in endometrium (P < 0.01). PGHS-1 concentration did not change after estradiol and/or progesterone administration (P > 0.05). PGHS-2 was immunolocalized in myometrial cells and endometrial glandular epithelial cells, whereas immunoreactive PGHS-1 was located in the myometrial cells, endothelial and smooth muscle cells of blood vessels, as well as epithelial cells of glands and stromal cells in endometrium. Estradiol-dependent activation of PGHS-2 gene expression resulted in increased PGHS-2 levels in sheep myometrium in vivo. Progesterone did not have any effect on PGHS-2 gene expression in the myometrium. In contrast, progesterone was a more potent stimulator of endometrial PGHS-2 abundance than estradiol. Estradiol and progesterone did not regulate PGHS-1 expression in either endometrium or myometrium. The distribution and differential regulation of PGHS-1 and -2 in myometrium and endometrium are consistent with the differential functions of both enzymes.

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