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

Ubiquitin cross-reactive protein (UCRP) is a functional ubiquitin homolog s ynthesized by the ruminant endometrium in response to conceptus-derived int erferon-tau (IFN tau). Progesterone is required for IFN tau to exert antilu teolytic actions on the endometrium. Therefore, this study was designed to determine whether progesterone is requisite for IFN tau induction of UCRP e xpression within the ovine uterus. Cyclic ewes were ovariectomized and fitt ed with intrauterine (i.u.) catheters on Day 5 and treated daily with stero ids (i.m.) and protein (i.u.) as follows: 1) progesterone (P, Days 5-24) an d control serum proteins (CX, Days 11-24); 2) P and ZK 137.316 (ZK; progest erone receptor antagonist, Days 11-24) and CX proteins; 3) P and recombinan t 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 induce d expression of UCRP mRNA in progestinized endometrial luminal (LE) and gla ndular (GE) epithelium as well as in both stratum compactum and spongiosum layers of the stroma (ST). Progesterone receptor protein was located in end ometrial ST, but not in LE and CE from these ewes. Results support the hypo thesis that progesterone is required for IFN tau induction of type I IFN-re sponsive genes, such as UCRP, in the ruminant uterus.