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12 June 2013 Intrauterine Inhibition of Prostaglandin Transporter Protein Blocks Release of Luteolytic PGF2alpha Pulses Without Suppressing Endometrial Expression of Estradiol or Oxytocin Receptor in Ruminants
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Abstract

In ruminants, prostaglandin F2 alpha (PGF2alpha) is synthesized and released in a pulsatile pattern from the endometria luminal epithelial (LE) cells during the process of luteolysis. Prostaglandin transporter (PGT) is a 12-transmembrane solute carrier organic anion transporter protein that facilitates transport of PGF2alpha. The present study determined the effects of inhibition of PGT protein on pulsatile release of luteolytic PGF2alpha and the underlined cell-signaling mechanisms. The results indicate that intrauterine inhibition of the PGT protein inhibits the pulsatile release of PGF2alpha from the endometrium and maintains a functional corpus luteum. Surprisingly, inhibition of PGT-mediated luteolytic pulses is not associated with spatial regulation of estrogen and oxytocin receptors in the LE of the endometrium and is also not accompanied by decreased biosynthesis of PGF2alpha or increased catabolism of PGF2alpha by the endometrium. Importantly, PGT inhibitor increases expression of pERK1/2 proteins in the LE of the endometrium. Knock down of ERK1/2 genes in LE cells reverses the inhibitory effects of PGT inhibitor on release of PGF2alpha. In conclusion, intrauterine inhibition of PGT inhibits the pulsatile release of PGF2alpha from the endometrium without modulating spatial expressions of estrogen and oxytocin receptor proteins and metabolism of PGF2alpha at the time of luteolysis. Activation of ERK1/2 pathways and interactions between ERK1/2 and PGT protein appear to be important cell-signaling mechanisms that control PGT-mediated efflux transport function. PGT emerges as an important final component in the luteolytic machinery that controls the release of luteolytic pulses of PGF2alpha from the endometrium in sheep.

JeHoon Lee, John A. McCracken, Sakhila K. Banu, and Joe A. Arosh "Intrauterine Inhibition of Prostaglandin Transporter Protein Blocks Release of Luteolytic PGF2alpha Pulses Without Suppressing Endometrial Expression of Estradiol or Oxytocin Receptor in Ruminants," Biology of Reproduction 89(2), (12 June 2013). https://doi.org/10.1095/biolreprod.112.106427
Received: 21 November 2012; Accepted: 1 May 2013; Published: 12 June 2013
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