Growth Hormone in the Brain: Characteristics of Specific Brain Targets for the Hormone and Their Functional Significance

Nyberg, Fred

doi:10.1006/frne.2000.0200

Cited by 219 publications

(185 citation statements)

References 84 publications

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“…In certain human brain tissues both the GHR protein, as assessed by receptor binding, and the GHR mRNA decrease by aging (15,16). In the present study, we did not observe any significant difference in hippocampal GHR or GHBP mRNA expression between untreated young and elderly adult male Sprague-Dawley rats.…”

Section: Discussioncontrasting

confidence: 67%

“…In one of these studies a dose-dependent increase in cerebrospinal fluid GH concentrations was confirmed (13). Further evidence for brain cells being targets for GH actions has emerged from the identification of specific receptors for the hormone in the brain (14,15). Because hippocampus is a brain region associated with the functional anatomy of memory and learning processes, it is of particular interest that a hippocampal GH-binding receptor has been identified and characterized in both humans (16) and rats (17).…”

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confidence: 99%

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Growth hormone induces age-dependent alteration in the expression of hippocampal growth hormone receptor and N -methyl- d -aspartate receptor subunits gene transcripts in male rats

Grevès

Steensland²,

Grevès³

et al. 2002

Proc. Natl. Acad. Sci. U.S.A.

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111

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Studies were conducted to evaluate the effects of s.c. injected recombinant human growth hormone (GH) on the expression of the gene transcript of N-methyl-D-aspartate receptor subunits type 1 (NR1), type 2A (NR2A), and type 2B (NR2B) in the male rat hippocampus. The GH-induced effects on the expression of hippocampal gene transcripts of GH receptor (GHR) and GH-binding protein were also examined. Male Sprague-Dawley rats, kept in four groups of two different ages, was treated with the hormone or saline during 10 days before decapitation and tissue dissection. Brain tissues collected were analyzed for mRNA content by using the Northern blot technique. The results indicated that in adult young rats (11 weeks of age) the hormone elicited a decrease in the mRNA expression of NR1 but an increase in that of the NR2B subunit. In elderly adult rats (57-67 weeks of age) GH induced an increase in the expression of the hippocampal message for NR1 and NR2A. Meanwhile, the hormone induced a significant up-regulation of the GHR transcript in hippocampus of adult young rats but not in elderly adult rats. It was further found that a significant positive correlation exists between the level of GHR mRNA and the expression of the NR2B subunit transcript in adult young rats. The GH-induced increase in the expression of hippocampal mRNA for the NR2B subunit is compatible with a previously observed memory promoting effect seen for the hormone, because overexpression of this N-methyl-D-aspartate receptor subunit is shown to enhance cognitive capabilities.

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Section: Discussioncontrasting

confidence: 67%

mentioning

confidence: 99%

Growth hormone induces age-dependent alteration in the expression of hippocampal growth hormone receptor and N -methyl- d -aspartate receptor subunits gene transcripts in male rats

Grevès

Steensland²,

Grevès³

et al. 2002

Proc. Natl. Acad. Sci. U.S.A.

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111

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“…Disruption of IGF‐1 gene expression during early life causes growth retardation and defects in the development of metabolic organs that can alter energy homeostasis throughout adult life (Woods et al ., 1996). GHR −/− mice have increased expression of hypothalamic IGF‐1 and IGF1R (Nyberg, 2000; Bartke, 2011), despite lower levels of plasma IGF‐1. Enhanced hypothalamic IGF‐1 expression in the mice with global disruption of GHR raises the possibility that compensatory increases in the local production and paracrine/autocrine actions of IGF‐1 could account for some characteristics of GH‐deficient mouse strains, because both GH and IGF‐1 exert neuroprotective effects (Sonntag et al ., 2005).…”

Section: Discussionmentioning

confidence: 99%

Growth hormone modulates hypothalamic inflammation in long‐lived pituitary dwarf mice

et al. 2015

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SummaryMice in which the genes for growth hormone (GH) or GH receptor (GHR −/−) are disrupted from conception are dwarfs, possess low levels of IGF‐1 and insulin, have low rates of cancer and diabetes, and are extremely long‐lived. Median longevity is also increased in mice with deletion of hypothalamic GH‐releasing hormone (GHRH), which leads to isolated GH deficiency. The remarkable extension of longevity in hypopituitary Ames dwarf mice can be reversed by a 6‐week course of GH injections started at the age of 2 weeks. Here, we demonstrate that mutations that interfere with GH production or response, in the Snell dwarf, Ames dwarf, or GHR −/− mice lead to reduced formation of both orexigenic agouti‐related peptide (AgRP) and anorexigenic proopiomelanocortin (POMC) projections to the main hypothalamic projection areas: the arcuate nucleus (ARH), paraventricular nucleus (PVH), and dorsomedial nucleus (DMH). These mutations also reduce hypothalamic inflammation in 18‐month‐old mice. GH injections, between 2 and 8 weeks of age, reversed both effects in Ames dwarf mice. Disruption of GHR specifically in liver (LiGHRKO), a mutation that reduces circulating IGF‐1 but does not lead to lifespan extension, had no effect on hypothalamic projections or inflammation, suggesting an effect of GH, rather than peripheral IGF‐1, on hypothalamic development. Hypothalamic leptin signaling, as monitored by induction of pStat3, is not impaired by GHR deficiency. Together, these results suggest that early‐life disruption of GH signaling produces long‐term hypothalamic changes that may contribute to the longevity of GH‐deficient and GH‐resistant mice.

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“…GH and ghrelin are important factors involved in the hypothalamic regulation of energy homoeostasis (Nyberg 2000, Nakazato et al 2001 and in functions ascribed to the hippocampus such as learning and memory processes (Diano et al 2006, Donahue et al 2006. These two brain areas express GHR mRNA (Bennett et al 1996, Minami et al 2006 in different cells types including astrocytes (Lobie et al 1993, Blackmore et al 2012.…”

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%

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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Growth Hormone in the Brain: Characteristics of Specific Brain Targets for the Hormone and Their Functional Significance

Cited by 219 publications

References 84 publications

Growth hormone induces age-dependent alteration in the expression of hippocampal growth hormone receptor and N -methyl- d -aspartate receptor subunits gene transcripts in male rats

Growth hormone induces age-dependent alteration in the expression of hippocampal growth hormone receptor and N -methyl- d -aspartate receptor subunits gene transcripts in male rats

Growth hormone modulates hypothalamic inflammation in long‐lived pituitary dwarf mice

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

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