Interferon-tau and progesterone regulate ubiquitin cross-reactive protein expression in the ovine uterus

Ubiquitin cross-reactive protein (UCRP) is a functional ubiquitin homolog synthesized by the ruminant endometrium in response to conceptus-derived interferon-tau (IFN tau). Progesterone is required for IFN tau to exert antiluteolytic actions on the endometrium. Therefore, this study was designed to determine whether progesterone is requisite for IFN tau induction of UCRP expression within the ovine uterus. Cyclic ewes were ovariectomized and fitted with intrauterine (i.u.) catheters on Day 5 and treated daily with steroids (i.m.) and protein (i.u.) as follows: 1) progesterone (P, Days 5-24) and control serum proteins (CX, Days 11-24); 2) P and ZK 137.316 (ZK; progesterone receptor antagonist, Days 11-24) and CX proteins; 3) P and recombinant ovine IFN tau (rolFN tau, Days 11-24); or 4) P and ZK and rolFN tau. All ewes were hysterectomized on Day 25. In P-treated ewes, rolFN tau increased endometrial UCRP mRNA and protein levels. However, administration of ZK to ewes ablated rolFN tau induction of UCRP. Recombinant ovine IFN tau induced expression of UCRP mRNA in progestinized endometrial luminal (LE) and glandular (GE) epithelium as well as in both stratum compactum and spongiosum layers of the stroma (ST). Progesterone receptor protein was located in endometrial ST, but not in LE and CE from these ewes. Results support the hypothesis that progesterone is required for IFN tau induction of type I IFN-responsive genes, such as UCRP, in the ruminant uterus.