title: Internalization and synaptogenic effect of GH in retinal ganglion cells (RGCs).
abstract: In the chicken embryo, GH gene expression occurs in the neural retina and retinal GH promotes cell survival and induces axonal growth of retinal ganglion cells. Neuroretinal GH is therefore of functional importance before the appearance of somatotrophs and the onset of pituitary GH secretion to the peripheral plasma (at ED15-17). Endocrine actions of pituitary GH in the development and function of the chicken embryo eye are, however, unknown. This possibility has therefore been investigated in ED15 embryos and using the quail neuroretinal derived cell line (QNR/D). During this research, we studied for the first time, the coexistence of exogenous (endocrine) and local GH (autocrine/paracrine) in retinal ganglion cells (RGCs). In ovo systemic injections of Cy3-labeled GH demonstrated that GH in the embryo bloodstream was translocated into the neural retina and internalized into RGC's. Pituitary GH may therefore be functionally involved in retinal development during late embryogenesis. Cy3-labelled GH was similarly internalized into QNR/D cells after its addition into incubation media. The uptake of exogenous GH was by a receptor-mediated mechanism and maximal after 30-60min. The exogenous (endocrine) GH induced STAT5 phosphorylation and increased growth associated protein 43 (GAP43) and SNAP-25 immunoreactivity. Ex ovo intravitreal injections of Cy3-GH in ED12 embryos resulted in GH internalization and STAT5 activation. Interestingly, the CY3-labeled GH accumulated in perinuclear regions of the QNR/D cells, but was not found in the cytoplasm of neurite outgrowths, in which endogenous retinal GH is located. This suggests that exogenous (endocrine) and local (autocrine/paracrine) GH are both involved in retinal function in late embryogenesis but they co-exist in separate intracellular compartments within retinal ganglion cells.
authors.affiliation: Department of Physiology, University of Alberta, Edmonton T6G 2H7, Canada.
authors.forename: Thomas
authors.initials: T
authors.lastname: Fleming
authors.affiliation: Department of Physiology, University of Alberta, Edmonton T6G 2H7, Canada; Departamento de Neurobiología Celular y Molecular, Instituto de Neurobiología, Campus Juriquilla, Universidad Nacional Autónoma de México, Querétaro, Qro. 76230, Mexico.
authors.forename: Carlos G
authors.initials: CG
authors.lastname: Martínez-Moreno
authors.affiliation: Departamento de Neurobiología Celular y Molecular, Instituto de Neurobiología, Campus Juriquilla, Universidad Nacional Autónoma de México, Querétaro, Qro. 76230, Mexico.
authors.forename: Janeth
authors.initials: J
authors.lastname: Mora
authors.affiliation: Department of Physiology, University of Alberta, Edmonton T6G 2H7, Canada.
authors.forename: Miray
authors.initials: M
authors.lastname: Aizouki
authors.affiliation: Departamento de Neurobiología Celular y Molecular, Instituto de Neurobiología, Campus Juriquilla, Universidad Nacional Autónoma de México, Querétaro, Qro. 76230, Mexico.
authors.forename: Maricela
authors.initials: M
authors.lastname: Luna
authors.affiliation: Departamento de Neurobiología Celular y Molecular, Instituto de Neurobiología, Campus Juriquilla, Universidad Nacional Autónoma de México, Querétaro, Qro. 76230, Mexico.
authors.forename: Carlos
authors.initials: C
authors.lastname: Arámburo
authors.affiliation: Department of Physiology, University of Alberta, Edmonton T6G 2H7, Canada. Electronic address: steve.harvey@ualberta.ca.
authors.forename: Steve
authors.initials: S
authors.lastname: Harvey
mesh_terms: D000818:Animals; D002645:Chickens; D013006:Growth Hormone / Q000378:metabolism*; D012160:Retina / Q000378:metabolism*; D012165:Retinal Ganglion Cells / Q000166:cytology / Q000378:metabolism*
chemical_list: D013006:Growth Hormone
keywords: Growth hormone; Neuroretina; Retinal ganglion cells; SNAP25; STAT5; Synaptogenesis