title: Growth hormone and prolactin regulate human neural stem cell regenerative activity.
abstract: We have previously shown that the growth hormone (GH)/prolactin (PRL) axis has a significant role in regulating neuroprotective and/or neurorestorative mechanisms in the brain and that these effects are mediated, at least partly, via actions on neural stem cells (NSCs). Here, using NSCs with properties of neurogenic radial glia derived from fetal human forebrains, we show that exogenously applied GH and PRL promote the proliferation of NSCs in the absence of epidermal growth factor or basic fibroblast growth factor. When applied to differentiating NSCs, they both induce neuronal progenitor proliferation, but only PRL has proliferative effects on glial progenitors. Both GH and PRL also promote NSC migration, particularly at higher concentrations. Since human GH activates both GH and PRL receptors, we hypothesized that at least some of these effects may be mediated via the latter. Migration studies using receptor-specific antagonists confirmed that GH signals via the PRL receptor promote migration. Mechanisms of receptor signaling in NSC proliferation, however, remain to be elucidated. In summary, GH and PRL have complex stimulatory and modulatory effects on NSC activity and as such may have a role in injury-related recovery processes in the brain.
authors.affiliation: Liggins Institute, University of Auckland, 2-6 Park Avenue, Grafton, Auckland, New Zealand. PathipatiP@neuropeds.ucsf.edu
authors.forename: P
authors.initials: P
authors.lastname: Pathipati
authors.forename: T
authors.initials: T
authors.lastname: Gorba
authors.forename: A
authors.initials: A
authors.lastname: Scheepens
authors.forename: V
authors.initials: V
authors.lastname: Goffin
authors.forename: Y
authors.initials: Y
authors.lastname: Sun
authors.forename: M
authors.initials: M
authors.lastname: Fraser
mesh_terms: D002465:Cell Movement; D049109:Cell Proliferation; D019382:Human Growth Hormone / Q000378:metabolism*; D006801:Humans; D058953:Neural Stem Cells / Q000378:metabolism*; D055495:Neurogenesis / Q000502:physiology*; D009474:Neurons / Q000378:metabolism; D011388:Prolactin / Q000378:metabolism*
chemical_list: D019382:Human Growth Hormone; D011388:Prolactin