Regulation of prostaglandin endoperoxide H synthase 1 and 2 by estradiol and progesterone in nonpregnant ovine myometrium and endometrium in vivo.
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 i.v. for 2 days (50 microg/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 microg/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.
Wu
W X
WX
Physiology Department, Cornell University College of Veterinary Medicine, Ithaca, New York 14853, USA.
Ma
X H
XH
Zhang
Q
Q
Buchwalder
L
L
Nathanielsz
P W
PW
D000818:Animals; D004717:Endometrium / Q000201:enzymology*; D004958:Estradiol / Q000008:administration & dosage / Q000494:pharmacology*; D005260:Female; D005786:Gene Expression Regulation / Q000187:drug effects*; D007150:Immunohistochemistry; D007527:Isoenzymes / Q000096:biosynthesis / Q000235:genetics*; D009215:Myometrium / Q000201:enzymology*; D010052:Ovariectomy; D011374:Progesterone / Q000008:administration & dosage / Q000494:pharmacology*; D011451:Prostaglandin-Endoperoxide Synthases / Q000096:biosynthesis / Q000235:genetics*; D012333:RNA, Messenger / Q000378:metabolism; D012756:Sheep
D007527:Isoenzymes; D012333:RNA, Messenger; D011374:Progesterone; D004958:Estradiol; D011451:Prostaglandin-Endoperoxide Synthases