Age-related reduction of human growth hormone-binding sites in the human brain

Lai, Zhennan; Roos, Paul; Zhai, Qing; Olsson, Yngve; Fhölenhag, Karin; Larsson, Christer; Nyberg, Fred

doi:10.1016/0006-8993(93)90114-3

Cited by 141 publications

(77 citation statements)

References 32 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: 62%

“…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). In a recent study we also described the nucleotide sequence of the cDNA for the GH receptor (GHR) in rat hippocampus (18).…”

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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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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: 62%

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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“…Preliminary reports in humans note that GHR mRNA has been detected in the choroid plexus (Nyberg 2000), in glioblastoma cells and in normal embryonic brain tissue (Zogopoulos et al 1996, Castro et al 2000. GH-binding activity in the choroid plexus, hippocampus, putamen, pituitary gland, and hypothalamus declines with advancing age (Lai et al 1993) and GHR mRNA declines in the choroid plexus (Nyberg 2000). This decline, in concert with the decline in circulating GH levels, may contribute to impaired mood and cognition in the elderly.…”

Section: Therapeutic Mechanisms: Neural Effectsmentioning

confidence: 99%

Growth hormone therapy and Quality of Life: possibilities, pitfalls and mechanisms

Hull

Harvey²

2003

Journal of Endocrinology

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The actions of growth hormone (GH) are not restricted to growth: GH modulates metabolic pathways as well as neural, reproductive, immune, cardiovascular, and pulmonary physiology. The importance of GH in most physiological systems suggests that GH deficiency at any age would be associated with significant morbidity. However, prior to the advent of recombinant GH, cadaverderived GH was only used therapeutically to correct the height deficit, and thereby hypothetically improve quality of life (QoL), in GH-deficient children. Physicians now have access to unlimited, albeit expensive, supplies of recombinant GH, and are considering the advisability of GH replacement or supplementation in other patient populations. This paper analyses studies investigating the relationship between GH and QoL in GH-deficient children or adults, in GH-replete short children suffering from idiopathic short stature, Turner syndrome, or intrauterine growth retardation and in GH-deficient or replete elderly adults. Possible mechanisms by which GH might improve QoL at neural and somatic sites are also proposed.

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“…Indeed, GHR isoforms exist, both in human brains and in rat brains (Lai et al 1993), which may mediate different functions in the CNS and periphery (Nyberg 2000). Furthermore, it cannot be excluded that although bGH is properly transcribed, the levels of final bioactive bGH peptide could be much lower.…”

Section: Discussionmentioning

confidence: 99%

Local overexpression of GH and GH/IGF1 effects in the adult mouse hippocampus

Walser¹,

Samà²,

Wickelgren³

et al. 2012

Journal of Endocrinology

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GH therapy improves hippocampal functions mainly via circulating IGF1. However, the roles of local GH and IGF1 expression are not well understood. We investigated whether transgenic (TG) overexpression in the adult brain of bovine GH (bGH) under the control of the glial fibrillary acidic protein (GFAP) promoter affected cellular proliferation and the expression of transcripts known to be induced by systemic GH in the hippocampus. Cellular proliferation was examined by 5-bromo-2 0 -deoxyuridine immunohistochemistry. Quantitative PCR and western blots were performed. Although robustly expressed, bGH-Tg did not increase either cell proliferation or survival. However, bGH-Tg modestly increased Igf1 and Gfap mRNAs, whereas other GH-associated transcripts were unaffected, i.e. the GH receptor (Ghr), IGF1 receptor (Igf1r), 2 0 ,3 0 -cyclic nucleotide 3 0 -phosphodiesterase (Cnp), ionotropic glutamate receptor 2a (Nr2a (Grin2a)), opioid receptor delta (Dor), synapse-associated protein 90/postsynaptic density-95-associated protein (Sapap2 (Dlgap2)), haemoglobin beta (Hbb) and glutamine synthetase (Gs (Glul )). However, IGF1R was correlated with the expression of Dor, Nr2a, Sapap2, Gs and Gfap. In summary, although local bGH expression was robust, it activated local IGF1 very modestly, which is probably the reason for the low response of previous GH-associated response parameters. This would, in turn, indicate that hippocampal GH is less important than endocrine GH. However, as most transcripts were correlated with the expression of IGF1R, there is still a possibility for endogenous circulating or local GH to act via IGF1R signalling. Possible reasons for the relative bio-inactivity of bGH include the bell-shaped dose-response curve and cell-specific expression of bGH.

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Age-related reduction of human growth hormone-binding sites in the human brain

Cited by 141 publications

References 32 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 therapy and Quality of Life: possibilities, pitfalls and mechanisms

Local overexpression of GH and GH/IGF1 effects in the adult mouse hippocampus

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