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    Growth hormone promotes proliferation of adult neurosphere cultures

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    Author
    McLenachan, S; Lum, M-G; Waters, MJ; Turnley, AM
    Date
    2009-06-01
    Source Title
    GROWTH HORMONE & IGF RESEARCH
    Publisher
    CHURCHILL LIVINGSTONE
    University of Melbourne Author/s
    Turnley, Ann; McLenachan, Samuel; LUM, MAY
    Affiliation
    Medicine, Dentistry And Health Sciences
    Metadata
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    Document Type
    Journal Article
    Citations
    McLenachan, S., Lum, M. -G., Waters, M. J. & Turnley, A. M. (2009). Growth hormone promotes proliferation of adult neurosphere cultures. GROWTH HORMONE & IGF RESEARCH, 19 (3), pp.212-218. https://doi.org/10.1016/j.ghir.2008.09.003.
    Access Status
    This item is currently not available from this repository
    URI
    http://hdl.handle.net/11343/26703
    DOI
    10.1016/j.ghir.2008.09.003
    Description

    C1 - Journal Articles Refereed

    Abstract
    OBJECTIVES: Growth hormone (GH) and its receptor (GHR) are widely expressed in the CNS. During development, GH signaling regulates both proliferation of neural progenitor cells as well as their differentiation into neurons and glia. Here we have examined the effect of GH signaling on adult subventricular zone derived neural progenitor cells cultured as neurospheres. DESIGN: GH was added to adult wild-type (WT) neurosphere cultures and neurosphere growth measured using the MTT cell proliferation assay. To examine the influence of endogenous GH production on neural progenitors, neurospheres derived from GH receptor knockout (GHRKO) mice were examined by measuring neurosphere sizes and Ki67 and TUNEL immunoreactivity. In addition, neurosphere growth curves were compared following long term culture. Finally, the differentiation of WT vs. GHRKO neurospheres was compared using immunocytochemistry for betaIII-tubulin and GFAP. RESULTS: While GH alone was insufficient to support neurosphere formation, it enhanced neurosphere growth by 20% in the presence of epidermal growth factor and fibroblast growth factor-2. Compared to wildtype neurospheres, GHRKO neurospheres were smaller, contained fewer proliferating cells and exhibited reduced self-renewal in long term culture. Addition of GH increased STAT5 phosphorylation levels in neurosphere cells. Upon differentiation, GHRKO neurospheres showed accelerated neurogenesis, although over time similar numbers of betaIII-tubulin positive neurons were generated by cells of both genotypes. CONCLUSIONS: GH functions as an autocrine mitogen in adult neurosphere cultures and promotes proliferation of neural progenitor cells as well as self-renewal of neurosphere cultures. In addition, signaling through the GHR appeared to delay neuronal differentiation in adult neurospheres.
    Keywords
    Regenerative Medicine (incl. Stem Cells and Tissue Engineering); Neurosciences not elsewhere classified; Nervous System and Disorders

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