The multidrug resistance-associated protein 4 (MRP4) appears as a functional carrier of prostaglandins regulated by oxytocin in the bovine endometrium.

Prostaglandins (PG) are involved in several female reproductive processes, and their action is regulated at the levels of biosynthesis, catabolism, and signal transduction. Facilitated transport across cell membranes emerges as an additional checkpoint regulating PG action. We have already reported on the influx transporter solute carrier organic anion transporting polypeptide (SLCO2A1) [PG transporter (PGT)] in relation to PG action in the bovine endometrium.

Epidermal growth factor receptor is an obligatory intermediate for oxytocin-induced cyclooxygenase 2 expression and prostaglandin F2 alpha production in bovine endometrial epithelial cells.

Oxytocin (OT) triggers the luteolytic pulses of prostaglandin F(2 alpha) (PGF(2 alpha)) from the endometrial epithelial cells in ruminants. We have proposed that the embryonic signal interferon-tau exerts its antiluteolytic effect by disrupting the OT signaling axis. Accordingly, we have attempted to define the signaling pathway of OT-induced PGF(2 alpha) production in the bovine endometrium using our newly characterized epithelial cell line (bEEL).

Oxytocin receptor down-regulation is not necessary for reducing oxytocin-induced prostaglandin F(2alpha) accumulation by interferon-tau in a bovine endometrial epithelial cell line.

Interferon-tau (IFNtau) is the embryonic signal responsible for pregnancy recognition in ruminants. The primary action of IFNtau is believed to be mediated through inhibition of prostaglandin F(2alpha) (PGF(2alpha)) released from the endometrial epithelial cells in response to oxytocin (OT). Our working hypothesis was that the antiluteolytic effect of IFNtau also involved modulation of PG production downstream of OT receptor (OTR) and/or cyclooxygenase 2 (COX2).

A postgenomic integrated view of prostaglandins in reproduction: implications for other body systems.

Prostaglandins are primary mediators of pain and are involved in pathological conditions such as hypertension, cancer and inflammation but are also needed for normal function of the female reproductive system. This may hold true for other systems because long term use of selective COX-2 inhibitors such as VIOXX and BEXTRA was associated with heart failure, leading to their withdrawal. A thorough study of the contribution of prostaglandins in the regulation of normal body function is clearly needed.