GnRH-(1-5) activates matrix metallopeptidase-9 to release epidermal growth factor and promote cellular invasion.

Abstract

In the extracellular space, the gonadotropin-releasing hormone (GnRH) is metabolized by the zinc metalloendopeptidase EC3.4.24.15 (EP24.15) to form the pentapeptide, GnRH-(1-5). GnRH-(1-5) diverges in function and mechanism of action from GnRH in the brain and periphery. GnRH-(1-5) acts on the orphan G protein-coupled receptor 101 (GPR101) to sequentially stimulate epidermal growth factor (EGF) release, phosphorylate the EGF receptor (EGFR), and facilitate cellular migration. These GnRH-(1-5) actions are dependent on matrix metallopeptidase (MMP) activity. Here, we demonstrated that these GnRH-(1-5) effects are dependent on increased MMP-9 enzymatic activity in the Ishikawa and ECC-1 cell lines. Furthermore, the effects of GnRH-(1-5) mediated by GPR101 and the subsequent increase in MMP-9 enzymatic activity lead to an increase in cellular invasion. These results suggest that GnRH-(1-5) and GPR101 regulation of MMP-9 may have physiological relevance in the metastatic potential of endometrial cancer cells.

• Authors: Madelaine Cho-Clark, Darwin O Larco, Brian R Zahn, Shaila K Mani, T John Wu
• Journal: Molecular and cellular endocrinology (Mol Cell Endocrinol) Vol. 415 Pg. 114-25 (Nov 05 2015) ISSN: 1872-8057 [Electronic] Ireland
• PMID: 26277400 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, Non-P.H.S.)
• Copyright: Published by Elsevier Ireland Ltd.

Chemical References

• GPR101 protein, human
• LHRH (1-5)
• Peptide Fragments
• Receptors, G-Protein-Coupled
• Gonadotropin-Releasing Hormone
• Epidermal Growth Factor
• MMP9 protein, human
• Matrix Metalloproteinase 9

Topics

• Cell Line, Tumor
• Cell Movement
• Endometrial Neoplasms (metabolism)
• Epidermal Growth Factor (metabolism)
• Female
• Gene Expression Regulation, Neoplastic
• Gonadotropin-Releasing Hormone (metabolism)
• Humans
• Matrix Metalloproteinase 9 (metabolism)
• Neoplasm Metastasis
• Peptide Fragments (metabolism)
• Phosphorylation
• Receptors, G-Protein-Coupled (genetics, metabolism)
• Signal Transduction