OVINE INTERFERON-TAU INHIBITS ESTROGEN-RECEPTOR UP-REGULATION AND ESTROGEN-INDUCED LUTEOLYSIS IN CYCLIC EWES

This study determined whether intrauterine injection of interferon-tau (IFN tau) could block luteolysis in cyclic ewes treated with a luteol ytic dose of 17 beta-estradiol benzoate (E) on day 12 of the estrous c ycle. Thirty-two ewes mere fitted with uterine catheters on day 5 of t he estrous cycle and treated with recombinant ovine IFN tau (2 x 10(7) antiviral units/ewe/day) or control proteins (6 mg/day) by intrauteri ne injection from day 10 until hysterectomy. At 1900 h on day 12, all ewes received 750 mu g E, im, and mere hysterectomized 12, 24, 36, or 48 h post-E administration. Plasma concentrations of progesterone decl ined in control animals but increased in IFN tau-treated ewes after E injection (P < 0.01, treatment x day interaction). Likewise, total cor pus luteum weight decreased in control but not IFN tau-treated ewes af ter E administration (P < 0.02, treatment x time interaction). In cont rol ewes, endometrial estrogen receptor (ER) messenger RNA (mRNA; P < 0.03) and progesterone receptor (PR) mRNA (P < 0.10) increased after 1 2 h, whereas concentrations of ER protein (P < 0.02) and PR protein (P < 0.04) increased after 24 h. In situ hybridization and immunohistoch emical analyses indicated that ER gene expression increased first in t he epithelium at 12 h and then in the stroma by 48 h, whereas PR gene expression first increased in the stroma and then in the epithelium. I n control ewes, endometrial oxytocin receptor (OTR) density increased (P < 0.10) after 12 h, with the largest increase occurring between 36- 48 h. In IFN tau-treated ewes, endometrial ER mRNA and protein and OTR density did not increase after E administration. Levels of PR mRNA in creased (P < 0.01) between 12-36 h, but decreased after 36 h. PR mRNA abundance increased between 12-36 h in the stroma, but not in the epit helium. Concentrations of PR protein were low and did not change in IF N tau-treated ewes. Immunoreactive PR protein was present at low level s in the stroma of all IFN tau-treated ewes. The results indicate that induction of luteolysis by E in control ewes involved sequential incr eases in endometrial ER mRNA and ER protein in the epithelium that pre ceded maximal increases in OTR density. Intrauterine injection of reco mbinant ovine IFN tau prevented luteolysis by inhibiting estrogen indu ced increases in endometrial ER and OTR gene expression.