Oxytocin receptor down-regulation is not necessary for reducing oxytocin-induced prostaglandin F2α accumulation by interferon-τ in a bovine endometrial epithelial cell line

Abstract

Interferon-τ-(IFNτ) is the embryonic signal responsible for pregnancy recognition in ruminants. The primary action of τFNt is believed to be mediated through inhibition of prostaglandin F2α (PGF2α) released from the endometrial epithelial cells in response to oxytocin (OT). Ourworking hypothesis was that the antiluteolytic effect of IFNτ also involved modulation of PG production downstream of OT receptor (OTR) and/or cyclooxygenase 2 (CO×2). There is currently no OT-sensitive endometrial cell line to study the molecular mechanisms underlying our hypotheses. Therefore, we established an immortalized bovine endometrial epithelial cell line (bEEL) exhibiting OT response. These cells were cytokeratin positive, expressed steroid receptors, and exhibited preferential accumulation of PGF2α over PGE2. The bEEL cells were highly sensitive to OT, showing time- and concentration-dependent increase in CO×2 transcript and protein and PGF2α accumulation. Interestingly, IFNτ (20 ng/ml) significantly reduced OT-induced PGF 2α accumulation, but surprisingly, the effect was not mediated through down-regulation of either OTR or CO×2. Rather, IFNτ up-regulated CO×2 in a time- and concentration-dependent manner while decreasing OT-induced PG accumulation. This suggests that CO×2 is not a primary target for the antiluteolytic effect of IFNτ. Because IFNt reduced OT-stimulated PGF2α accumulation within 3 h, the mechanism likely involves a direct interference atthe level of the OTsignaling ortranscription in additiontothe down-regulation of OTR observed in vivo. In summary, bEEL cells offer a unique in vitro model for investigating the cellular and molecular mechanisms underlying O Tand IFNτ response in relation with luteolysis and recognition of pregnancy in the bovine. Copyright © 2009 by The Endocrine Society.