Growth Hormone (GH) and GH-Releasing Peptide-6 Increase Brain Insulin-Like Growth Factor-I Expression and Activate Intracellular Signaling Pathways Involved in Neuroprotection

Frago, Laura M.; Pañeda, Covadonga; Dickson, Suzanne L.; Hewson, A. K.; Argente, Jesús; Chowen, Julie A.

doi:10.1210/en.2002-220261

Cited by 119 publications

(97 citation statements)

References 74 publications

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“…Treatment with GHRP-6 did not increase GFAP levels but stimulated proliferation in the hypothalamus and hippocampus. GHRP-6 and ghrelin stimulate the proliferation of a wide number of cells including osteoblasts (Kim et al 2005), cardiomyocytes (Pettersson et al 2002), somatotrophs (Dieguez & Casanueva 2000), endothelial cells (Rossi et al 2009) and adipocytes (Thompson et al 2004) and may also affect the CNS by protecting neurons from apoptosis (Frago et al 2002, 2011, Delgado-Rubin de Célix et al 2006, Delgado-Rubin et al 2009). We also evaluated the possible effect of GH and GHRP-6 on neuron number and did not observed any changes in the levels of Tuj1 in the hypothalamus or hippocampus.…”

Section: Discussionmentioning

confidence: 99%

“…It is well established that GH, one of the main regulators of growth and metabolism (Conway-Campbell et al 2007, Lichanska & Waters 2008, also has profound effects in the CNS (Harvey et al 1993, Nyberg 2000, Donahue et al 2006, being involved in the regulation of emotion (Burman & Deijen 1998), cognitive functions, memory (Deijen et al 2011), appetite (Stoving et al 1999) and neuroprotection (Scheepens et al 1999, Frago et al 2002, Lyuh et al 2007. Indeed, the GH receptor (GHR) is expressed in diverse areas throughout the CNS (Fraser et al 1990, Le Greves et al 2005 where this hormone has been shown to be involved in numerous cellular activities such as stimulation of mitosis, cell proliferation and differentiation (Frago et al 2002, Ajo et al 2003.…”

Section: Introductionmentioning

confidence: 99%

“…Indeed, the GH receptor (GHR) is expressed in diverse areas throughout the CNS (Fraser et al 1990, Le Greves et al 2005 where this hormone has been shown to be involved in numerous cellular activities such as stimulation of mitosis, cell proliferation and differentiation (Frago et al 2002, Ajo et al 2003. Binding of GH to its receptor mediates many of its effects through activation of the JAK/STAT signalling pathway (Lanning & Carter-Su 2006); however, GHR is also able to signal through additional pathways including the MAPK and the phosphatidylinositol 3 0 -kinase (PI3K; Brooks et al 2008) pathways.…”

Section: Introductionmentioning

confidence: 99%

“…GRLN-R1a activation leads to an increase in intracellular levels of Ca 2C via phosphatidylinositol-specific phospholipase C (Camiña et al 2003, Muccioli et al 2007). Ghrelin and GHRP-6 stimulate proliferation of different cell types (Dieguez & Casanueva 2000, Pettersson et al 2002, Thompson et al 2004, Rossi et al 2009) and may also affect the CNS by protecting neurons from apoptosis (Frago et al 2002, 2011, Delgado-Rubin de Célix et al 2006, Delgado-Rubin et al 2009). …”

Section: Introductionmentioning

confidence: 99%

“…In addition, as rats treated with GH or GHRP-6 showed increased levels of phosphorylated Akt in the hypothalamus, hippocampus and cerebellum, but not of ERKs1/2 (Frago et al 2002), and Akt is a central regulator of survival, growth and proliferation (Pascual & Guerri 2007), we evaluated the possible involvement of Akt in these processes.…”

Section: Introductionmentioning

confidence: 99%

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Differential effects of GH and GH-releasing peptide-6 on astrocytes

Baquedano¹,

Chowen²,

Argente³

et al. 2013

Journal of Endocrinology

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GH and GH secretagogues (GHSs) are involved in many cellular activities such as stimulation of mitosis, proliferation and differentiation. As astrocytes are involved in developmental and protective functions, our aim was to analyse the effects of GH and GH-releasing hexapeptide on astrocyte proliferation and differentiation in the hypothalamus and hippocampus. Treatment of adult male Wistar rats with GH (i.v., 100 mg/day) for 1 week increased the levels of glial fibrillary acidic protein (GFAP) and decreased the levels of vimentin in the hypothalamus and hippocampus. These changes were not accompanied by increased proliferation. By contrast, GH-releasing hexapeptide (i.v., 150 mg/day) did not affect GFAP levels but increased proliferation in the areas studied. To further study the intracellular mechanisms involved in these effects, we treated C6 astrocytoma cells with GH or GH-releasing hexapeptide and the phosphatidylinositol 3 0 -kinase (PI3K) inhibitor, LY294002, and observed that the presence of this inhibitor reverted the increase in GFAP levels induced by GH and the proliferation induced by GH-releasing hexapeptide. We conclude that although GH-releasing hexapeptide is a GHS, it may exert GH-independent effects centrally on astrocytes when administered i.v., although the effects of both substances appear to be mediated by the PI3K/Akt pathway.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 3 more Smart Citations

Differential effects of GH and GH-releasing peptide-6 on astrocytes

Baquedano¹,

Chowen²,

Argente³

et al. 2013

Journal of Endocrinology

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Peptide hormones as developmental growth and differentiation factors

Sanders

Harvey

2008

Developmental Dynamics

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Peptide hormones, usually considered to be endocrine factors responsible for communication between tissues remotely located from each other, are increasingly being found to be synthesized in developing tissues, where they act locally. Several hormones are now known to be produced in developing tissues that are unrelated to the endocrine gland of origin in the adult. These hormones are synthesized locally, and are active as differentiation and survival factors, before the developing adult endocrine tissue becomes functional. There is increasing evidence for paracrine and/or autocrine actions for these factors during development, thus, placing them among the conventional growth and differentiation factors. We review the evidence for the view that thyroid hormones, growth hormone, prolactin, insulin, and parathyroid hormone-related protein are developmental growth and differentiation factors. Developmental Dynamics 237:1537-1552, 2008.

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Insulin‐like growth factor‐I increases astrocyte intercellular gap junctional communication and connexin43 expression in vitro

Åberg

Blomstrand

Åberg

et al. 2003

J of Neuroscience Research

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Connexin43 (cx43) forms gap junctions in astrocytes, and these gap junctions mediate intercellular communication by providing transport of low-molecular-weight metabolites and ions. We have recently shown that systemic growth hormone increases cx43 in the brain. One possibility was that local brain insulin-like growth factor-I (IGF-I) could mediate the effect by acting directly on astrocytes. In the present study, we examined the effects of direct application of recombinant human IGF-I (rhIGF-I) on astrocytes in primary culture concerning cx43 protein expression and gap junctional communication (GJC). After 24 hr of stimulation with rhIGF-I under serum-free conditions, the GJC and cx43 protein were analyzed. Administration of 30 ng/ml rhIGF-I increased the GJC and the abundance of cx43 protein. Cell proliferation of the astrocytes was not significantly increased by rhIGF-I at this concentration. However, a higher concentration of rhIGF-I (150 ng/ml) had no effect on GJC/cx43 but increased cell proliferation. Because of the important modulatory role of IGF binding proteins (IGFBPs) on IGF-I action, we analyzed IGFBPs in conditioned media. In cultures with a low abundance of IGFBPs (especially IGFBP-2), the GJC response to 30 ng/ml rhIGF-I was 81%, compared with the average of 25%. Finally, as a control, insulin was given in equimolar concentrations. However, GJC was not affected, which suggests that rhIGF-I acted via IGF-I receptors. In summary, the data show that rhIGF-I may increase GJC/cx43, whereas a higher concentration of rhIGF-I--at which stimulation of proliferation occurred--did not affect GJC/cx43. Furthermore, IGFBP-2 appeared to modulate the action of rhIGF-I on GJC in astrocytes by a paracrine mechanism.

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Growth Hormone (GH) and GH-Releasing Peptide-6 Increase Brain Insulin-Like Growth Factor-I Expression and Activate Intracellular Signaling Pathways Involved in Neuroprotection

Cited by 119 publications

References 74 publications

Differential effects of GH and GH-releasing peptide-6 on astrocytes

Differential effects of GH and GH-releasing peptide-6 on astrocytes

Peptide hormones as developmental growth and differentiation factors

Insulin‐like growth factor‐I increases astrocyte intercellular gap junctional communication and connexin43 expression in vitro

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