title: High level of GHR nuclear translocation in skeletal muscle of a hyperplasic transgenic zebrafish.
abstract: It has been reported that nuclear translocation of growth hormone receptor (GHR) may directly activate cell proliferation in mammals and birds. However, this phenomenon has not yet been described in fish. Recently, we have developed a transgenic zebrafish that overexpresses GHR in a muscle-specific manner. Considering that this transgenic model exhibits hyperplasic muscle growth, the present work aims at verifying the relationship between GHR nuclear translocation and muscle cell proliferation. This relationship was evaluated by the phosphorylation state of the proliferative MEK/ERK pathway, expression of nuclear import-related genes, immunostaining of phospho-histone H3 (PH3) as a proliferation marker, and nuclear GHR localization. The results showed a significant decrease in the phosphorylation state of ERK1/2 proteins in transgenics. Moreover, there was an increase in expression of three out of four importin genes analyzed parallel to a large flow of GHR displacement toward and into the nucleus of transgenic muscle cells. Also, transgenics presented a marked increase in PH3 staining, which indicates cell proliferation. These findings, as far as we know, are the first report suggesting a proliferative action of GHR in fish as a consequence of its increased nuclear translocation. Thus, it appears that the nuclear migration of cytokine receptors is a common event among different taxonomic groups. In addition, the results presented here highlight the possibility that these membrane proteins may be involved more directly than previously thought in the control of genes related to cell growth and proliferation.
authors.affiliation: Laboratório de Biologia MolecularInstituto de Ciências Biológicas, Universidade Federal do Rio Grande - FURG, Avenue Italia, Km 8, CEP 96203-900, Rio Grande, RS, BrazilLaboratório de Cultura CelularInstituto de Ciências Biológicas, Universidade Federal do Rio Grande - FURG, Rio Grande, RS, BrazilLaboratório de HistologiaInstituto de Ciências Biológicas, Universidade Federal do Rio Grande - FURG, Rio Grande, RS, Brazil.
authors.forename: Marcio A
authors.initials: MA
authors.lastname: Figueiredo
authors.affiliation: Laboratório de Biologia MolecularInstituto de Ciências Biológicas, Universidade Federal do Rio Grande - FURG, Avenue Italia, Km 8, CEP 96203-900, Rio Grande, RS, BrazilLaboratório de Cultura CelularInstituto de Ciências Biológicas, Universidade Federal do Rio Grande - FURG, Rio Grande, RS, BrazilLaboratório de HistologiaInstituto de Ciências Biológicas, Universidade Federal do Rio Grande - FURG, Rio Grande, RS, Brazil.
authors.forename: Robert T
authors.initials: RT
authors.lastname: Boyle
authors.affiliation: Laboratório de Biologia MolecularInstituto de Ciências Biológicas, Universidade Federal do Rio Grande - FURG, Avenue Italia, Km 8, CEP 96203-900, Rio Grande, RS, BrazilLaboratório de Cultura CelularInstituto de Ciências Biológicas, Universidade Federal do Rio Grande - FURG, Rio Grande, RS, BrazilLaboratório de HistologiaInstituto de Ciências Biológicas, Universidade Federal do Rio Grande - FURG, Rio Grande, RS, Brazil.
authors.forename: Juliana Z
authors.initials: JZ
authors.lastname: Sandrini
authors.affiliation: Laboratório de Biologia MolecularInstituto de Ciências Biológicas, Universidade Federal do Rio Grande - FURG, Avenue Italia, Km 8, CEP 96203-900, Rio Grande, RS, BrazilLaboratório de Cultura CelularInstituto de Ciências Biológicas, Universidade Federal do Rio Grande - FURG, Rio Grande, RS, BrazilLaboratório de HistologiaInstituto de Ciências Biológicas, Universidade Federal do Rio Grande - FURG, Rio Grande, RS, Brazil.
authors.forename: Antonio S
authors.initials: AS
authors.lastname: Varela
authors.affiliation: Laboratório de Biologia MolecularInstituto de Ciências Biológicas, Universidade Federal do Rio Grande - FURG, Avenue Italia, Km 8, CEP 96203-900, Rio Grande, RS, BrazilLaboratório de Cultura CelularInstituto de Ciências Biológicas, Universidade Federal do Rio Grande - FURG, Rio Grande, RS, BrazilLaboratório de HistologiaInstituto de Ciências Biológicas, Universidade Federal do Rio Grande - FURG, Rio Grande, RS, Brazil dqmluf@furg.br.
authors.forename: Luis F
authors.initials: LF
authors.lastname: Marins
mesh_terms: D021581:Active Transport, Cell Nucleus; D000818:Animals; D030801:Animals, Genetically Modified; D006965:Hyperplasia / Q000378:metabolism; D020935:MAP Kinase Signaling System; D018482:Muscle, Skeletal / Q000378:metabolism* / Q000473:pathology; D011986:Receptors, Somatotropin / Q000378:metabolism*; D015027:Zebrafish
chemical_list: D011986:Receptors, Somatotropin
keywords: Danio rerio; growth hormone receptor; hyperplasia; nuclear transport