REGULATION OF PROSTAGLANDIN ENDOPEROXIDE-H SYNTHASE-1 AND SYNTHASE-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 te rm labor. In this study, we examined estradiol and progesterone regula tion in vivo of PGHS-1 and PGHS-2 expression at both mRNA and protein levels using a nonpregnant ovariectomized sheep model. We determined t he differential distribution of PGHS-2 and PGHS-1 in ovine myometrium and endometrium with immunocytochemistry. Twenty ovariectomized ewes w ere treated with saline (n = 5) or estradiol infused iv for 2 days (50 mu g/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 mu g/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 a nalyses, respectively. PGHS-2 mRNA and protein abundance increased sig nificantly in myometrium after estradiol treatment (P < 0.01). In cont rast, progesterone was a more potent stimulator than estradiol of PGHS -2 protein abundance in endometrium (P < 0.01). PGHS-1 concentration d id 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 en dometrium. Estradiol-dependent activation of PGHS-2 gene expression re sulted in increased PGHS-2 levels in sheep myometrium in vivo. Progest erone did not have any effect on PGHS-2 gene expression in the myometr ium. In contrast, progesterone was a more potent stimulator of endomet rial PGHS-2 abundance than estradiol. Estradiol and progesterone did n ot regulate PGHS-1 expression in either endometrium or myometrium. The distribution and differential regulation of PGHS-1 and -2 in myometri um and endometrium are consistent with the differential functions of b oth enzymes.