TAILIEUCHUNG - Báo cáo khoa học: Gonadotropin-releasing hormone: GnRH receptor signaling in extrapituitary tissues

Gonadotropin-releasing hormone (GnRH) has historically been known as a pituitary hormone; however, in the past few years, interest has been raised in locally produced, extrapituitary GnRH. GnRH receptor (GnRHR) was found to be expressed in normal human reproductive tissues (. breast, endometrium, ovary, and prostate) and tumors derived from these tissues. | ỊFEBS Journal MINIREVIEW Gonadotropin-releasing hormone GnRH receptor signaling in extrapituitary tissues Lydia W. T. Cheung and Alice S. T. Wong Schoolof BiologicalSciences University of Hong Kong China Keywords cross-talk extrapituitary GnRH GnRH receptor MARK metastasis pituitary receptor tyrosine kinase signaling tumor Correspondence A. S. T. Wong Schoolof Biological Sciences University of Hong Kong 4S-14 Kadoorie BiologicalSciences Building Rokfulam Road Hong Kong China Fax 852 2559 9114 Tel 852 2299 0865 E-mail awong1@ Received 14 April2008 revised 28 May 2008 accepted 11 June 2008 doi Gonadotropin-releasing hormone GnRH has historically been known as a pituitary hormone however in the past few years interest has been raised in locally produced extrapituitary GnRH. GnRH receptor GnRHR was found to be expressed in normal human reproductive tissues . breast endometrium ovary and prostate and tumors derived from these tissues. Numerous studies have provided evidence for a role of GnRH in cell proliferation. More recently we and others have reported a novel role for GnRH in other aspects of tumor progression such as metastasis and angiogenesis. The multiple actions of GnRH could be linked to the divergence of signaling pathways that are activated by GnRHR. Recent observations also demonstrate cross-talk between GnRHR and growth factor receptors. Intriguingly the classical Gaq-11-phospholipase C signal transduction pathway known to function in pituitary gonadotropes is not involved in GnRH actions at nonpituitary targets. Herein we review the key findings on the role of GnRH in the control of tumor growth progression and dissemination. The emerging role of GnRHR in actin cytoskeleton remodeling small Rho GTPases expression and or activity of adhesion molecules integrins proteolytic enzymes matrix metalloproteinases and angiogenic factors is explored. The signal transduction mechanisms of GnRHR in mediating these activities

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