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BOR - Papers in Press, published online ahead of print October 17, 2002.
Biol Reprod 2002, 10.1095/biolreprod.102.007625
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Submitted May 27, 2002
Returned for revision June 11, 2002
Accepted August 22, 2002

Female Reproductive Tract


Signal Transduction Pathways Activated by Chorionic Gonadotropin in Primate Endometrial Epithelial Cells

Santha Srisuparp 1, Zuzana Strakova 2, Allison Brudney 3, Sutapa Mukherjee 4, Scott Reierstad 5, Mary Hunzicker-Dunn 4, Asgerally T. Fazleabas 2*
1 University of Illinois
2 University of Illinois at Chicago
3 University of Illinis at Chicago
4 Northwestern University Medical School
5 Northwestern U Med School

* To whom correspondence should be addressed. E-mail: asgi{at}uic.edu.

Abstract

Successful implantation requires synergism between the developing embryo and the receptive endometrium. In the baboon, infusion of CG modulates both morphology and physiology of the epithelial and stromal cells of the receptive endometrium. This study explored the signal transduction pathways activated by CG in endometrial epithelial cells from baboon (BE) and human (HES). Incubations of BE and HES cells with CG did not significantly alter adenylyl cyclase activity or increase intracellular cAMP, when compared to Chinese hamster ovarian cells stably transfected with the full-length human CG/ luteinizing hormone (LH) receptor (CHO-LH cells). However, in BE and HES cells CG induced the phosphorylation of several proteins, among them extracellular signal regulated protein kinases 1 and 2 (ERK 1/2). Phosphorylation of ERK 1/2 in uterine epithelial cells was protein kinase A (PKA) independent. This novel signaling pathway is functional since in response to CG stimulation prostaglandin E2 (PGE2) was released into the media and increased significantly 2 h following CG stimulation. CG-stimulated PGE2 synthesis in epithelial cells was inhibited by a specific mitogen activated protein kinase kinase (MEK 1/2) inhibitor, PD 98059. In conclusion, immediate signal transduction pathways induced by CG in endometrial epithelial cells are cAMP independent and stimulate phosphorylation of ERK 1/2 via a MEK 1/2 pathway leading to an increase in PGE2 release as possible result of COX-2 activation.



Key words: Human chorionic gonadotropin • Signal transduction • Uterus


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