Mammalian gonadotropin-releasing hormone (GnRH-I), a decapeptide that is typically produced by hypothalamic neurosecretory cells, plays key roles in the processes of reproduction. A second GnRH subtype (GnRH-II) also has been identified in humans. In addition to their well-known endocrine function, it has become evident that GnRH-I and GnRH-II are important autocrine and/or paracrine regulators of trophoblasts behavior during the processes of embryo implantation and placentation. However, the signaling pathways of these two types of GnRH in regulating trophoblast cell invasion remains unclear.
The research groups led by Professor Yan-ling Wang at the Institute of Zoology, Chinese Academy of Sciences, in collaboration with Professor Peter C.K. Leung at the University of British Columbia in Canada, investigated the molecular mechanisms underlying GnRH-I and II-stimulated cell invasion in the primary cultured human trophoblasts. They found that both GnRH-I and GnRH-II activated PKC, ERK1/2 and JNK to mediate their effects on trophoblast invasion, while GnRH-II, but not GnRH-I, elicited invasion-promoting action through transactivating the tyrosine kinase activity of EGF receptor in trophoblasts. The knockdown of GnRH receptor by the specific siRNA led to the inhibition of the regulatory effects of GnRH I, but not that of GnRH II on trophoblast invasion. The data suggested the existence of a novel binding protein or receptor for GnRH II. Their observations elucidate a ligand-dependent selective cross-communication between GnRH receptor and EGF receptor signaling systems in human trophoblastic cell, and this will further our understanding on the differentially biological significance of these two forms of GnRH in extrapituitary tissues.
The results of this study were recently published in Molecular Endocrinology (Liu J, MacCalman CD, Wang YL, Leung PC. Molecular Endocrinology. 2009, 23(7):1014-1021). The work was supported by the Chinese National Special Fund for Basic Research Project (No. 2006CB944008) and the Knowledge Innovation Program in Chinese Academy of Sciences (Grant No. KSCX2-YW-R-53).
The 5th International Conference on Rodent Biol...
