The prostaglandin transporter (PGT) as a potential mediator of ovulation (May 2016)

The prostaglandin transporter (PGT) as a potential mediator of ovulation
Science Translational Medicine 11 May 2016;Vol. 8, Issue 338, pp.
Yerushalmi GM1, Markman S1, Yung Y1, Maman E1, Aviel-Ronen S2, Orvieto R1, Adashi EY3, Hourvitz A1
Author(s) affiliation:
1IVF Unit and Reproduction Laboratory, Department of Obstetrics and Gynecology, Chaim Sheba Medical Center, Tel Hashomer 5262100, affiliated with the Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv 6997801, Israel.
2Department of Pathology, Talpiot Medical Leadership Program, Chaim Sheba Medical Center, Tel Hashomer, affiliated with the Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv 6997801, Israel.
3Department of Obstetrics and Gynecology, Warren Alpert Medical School, Brown University, Providence, RI 02906, USA.


Short description:
Prostaglandins are known to play an important role in ovulation, but the role of prostaglandin transporter, a protein that transports prostaglandins across the cell membrane, was not well understood. By studying the process of ovulation in human cells and in mouse models, Yerushalmi et al. found that the activity of the prostaglandin transporter regulates the extracellular concentration of prostaglandin E2 in the ovarian follicles and thereby determines whether ovulation will occur. The authors also showed that inhibiting this transporter blocks ovulation in mice, suggesting that this approach may be a feasible method of contraception if these results are confirmed in humans.
Link to the journal


Abstract taken from PubMed

Prostaglandins (PGs) play an important role in the ovulatory process. However, the role of the PG transporter (PGT) in this context remains unknown. We report that the expression of PGT, a transmembrane PG carrier protein, is markedly up-regulated in preovulatory human granulosa cells (GCs). Treatment with human chorionic gonadotropin (hCG), an ovulatory trigger, significantly increases the expression of PGT mRNA and protein in human GCs both in vivo and in vitro. The hCG-induced increase in the expression of PGT in cultured human GCs is mediated via protein kinase A and protein kinase C by way of the extracellular signal-regulated kinase pathway. PGT in cultured human GCs mediates the uptake of PGE2, thereby regulating its extracellular concentration. In vivo treatment of mice with PGT inhibitors effectively blocks ovulation and markedly attenuates the expression of key ovulatory genes. We hypothesize that the inhibition of PGT activity in GCs increases the extracellular concentration of PGE2, the ability of which to exert its ovulatory effect is compromised by desensitization of its cognate receptors. Together, these findings support the idea that PGT is an important mediator of ovulation and that its inhibitors may be viewed as potential candidates for nonhormonal contraception. These findings may also fill the gap in the understanding of PGT signaling, enhance the understanding of ovulatory disorders, and facilitate the treatment of infertility or subfertility in women by using nonsteroidal PG-based therapeutic approaches.

Copyright © 2016, American Association for the Advancement of Science.
Link to the paper on PubMed


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