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Role of Endothelin-1 in the Migration of Human Olfactory Gonadotropin-Releasing Hormone-Secreting Neuroblasts

Departments of Anatomy Histology and Forensic Medicine (A.P., S.A., M.M., G.B.V.), Clinical Physiopathology and Endocrinology (R.S., C.M.R.), and Andrology Units (M.M., M.L., A.M.), Internal Medicine (R.G.R.), and Preclinical and Clinical Pharmacology (P.F.), University of Florence, I-50134 Florence; Department of Endocrinology (R.M., R.Z.), University of Milan, 20133 Milan; and Experimental and Clinical Medicine (T.B.), University of Catanzaro, 88100 Catanzaro, Italy

Address all correspondence and requests for reprints to: Gabriella B. Vannelli, Department of Anatomy Histology and Forensic Medicine, University of Florence, School of Medicine, V. le Morgagni 85, I-50134 Florence, Italy. E-mail: vannelli{at}unifi.it.

FNC-B4 neuroblasts that express both neuronal and olfactory markers have been established and cloned. These cells express GnRH and both the endothelin-1 (ET-1) gene and protein and respond in a migratory manner to GnRH in a dose-dependent manner. Previous research has shown that FNC-B4 cells produce and respond to ET-1 by regulating the secretion of GnRH through endothelin type A receptors and by stimulating their proliferation through endothelin type B (ETB) receptors. In this study, we found that FNC-B4 cells are able to migrate in response to ET-1 through the involvement of ETB receptors. Combined immunohistochemical and biochemical analyses showed that ET-1 triggered actin cytoskeletal remodeling and a dose-dependent increase in migration (up to 6-fold). Whereas the ETB receptor antagonist (B-BQ788) blunted the ET-1-induced effects, the ETA receptor antagonist (A-BQ123) did not. Moreover, we observed that FNC-B4 cells were independently and selectively stimulated by ET-1 and GnRH. We suggest that ET-1, through ETB receptor activation, may be required to maintain an adequate proliferative stem cell pool in the developing olfactory epithelium and the subsequent commitment to GnRH neuronal migratory pattern. The coordinate interaction between ET receptors and GnRH receptor participates in the fully expressed GnRH-secreting neuron phenotype.

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				S. A. Tobet and G. A. Schwarting Minireview: Recent Progress in Gonadotropin-Releasing Hormone Neuronal Migration Endocrinology, March 1, 2006; 147(3): 1159 - 1165. [Abstract] [Full Text] [PDF]