Growth Hormone (GH) and Gonadotropin-Releasing Hormone (GnRH) in the Central Nervous System: A Potential Neurological Combinatory Therapy?

Martínez-Moreno, Carlos G.; Calderón-Vallejo, Denisse; Harvey, S.; Arámburo, Carlos; Quintanar, J. Luis

doi:10.3390/ijms19020375

Cited by 43 publications

(29 citation statements)

References 193 publications

(233 reference statements)

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“…Growth hormone (GH) is a mitogenic peptide synthetized and released by somatotrophic cells in the pituitary gland. In addition, GH can be synthetized and released by neurons within the CNS, where it participates in stress-response and neuroprotection ( Martínez-Moreno et al, 2018 ). In the human retina, GH and GH receptors (GHR) are expressed in RGCs, where the existence of RGC autocrine regulation by GH has been hypothesized ( Sanders et al, 2006 , 2009 ; Harvey et al, 2009 ).…”

Section: Neurotrophic/growth Factors (Neuronal Vascular or Both)mentioning

confidence: 99%

The Role of Endogenous Neuroprotective Mechanisms in the Prevention of Retinal Ganglion Cells Degeneration

et al. 2018

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Retinal neurons are not able to undergo spontaneous regeneration in response to damage. A variety of stressors, i.e., UV radiation, high temperature, ischemia, allergens, and others, induce reactive oxygen species production, resulting in consecutive alteration of stress-response gene expression and finally can lead to cell apoptosis. Neurons have developed their own endogenous cellular protective systems. Some of them are preventing cell death and others are allowing functional recovery after injury. The high efficiency of these mechanisms is crucial for cell survival. In this review we focus on the contribution of the most recently studied endogenous neuroprotective factors involved in retinal ganglion cell (RGC) survival, among which, neurotrophic factors and their signaling pathways, processes regulating the redox status, and different pathways regulating cell death are the most important. Additionally, we summarize currently ongoing clinical trials for therapies for RGC degeneration and optic neuropathies, including glaucoma. Knowledge of the endogenous cellular protective mechanisms may help in the development of effective therapies and potential novel therapeutic targets in order to achieve progress in the treatment of retinal and optic nerve diseases.

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Section: Neurotrophic/growth Factors (Neuronal Vascular or Both)mentioning

confidence: 99%

The Role of Endogenous Neuroprotective Mechanisms in the Prevention of Retinal Ganglion Cells Degeneration

et al. 2018

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“…1,2 Regarding the neural effects of GH, it has been shown recently that its clinical application has revealed promising results as a treatment for stroke, spinal cord injury, brain trauma, and neurodegenerative diseases. 3,4 Also, important neurotrophic actions of GH in the neuroretina are related with the modulation of developmental apoptosis and neuroprotection, 5,6 because it has been observed that exogenous GH administration protects against experimental excitotoxic damage. 7,8 In addition, GH acts during neural differentiation and network establishment to promote axon growth 9,10 and synaptogenesis.…”

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confidence: 99%

Growth Hormone Neuroprotection Against Kainate Excitotoxicity in the Retina is Mediated by Notch/PTEN/Akt Signaling

Fleming

Balderas-Márquez

Epardo

et al. 2019

Invest. Ophthalmol. Vis. Sci.

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In the retina, growth hormone (GH) promotes axonal growth, synaptic restoration, and protective actions against excitotoxicity. Notch signaling pathway is critical for neural development and participates in the retinal neuroregenerative process. We investigated the interaction of GH with Notch signaling pathway during its neuroprotective effect against excitotoxic damage in the chicken retina. METHODS. Kainate (KA) was used as excitotoxic agent and changes in the mRNA expression of several signaling markers were determined by qPCR. Also, changes in phosphorylation and immunoreactivity were determined by Western blotting. Histology and immunohistochemistry were performed for morphometric analysis. Overexpression of GH was performed in the quail neuroretinal-derived immortalized cell line (QNR/D) cell line. Exogenous GH was administered to retinal primary cell cultures to study the activation of signaling pathways. RESULTS. KA disrupted the retinal cytoarchitecture and induced significant cell loss in several retinal layers, but the coaddition of GH effectively prevented these adverse effects. We showed that GH upregulates the Notch signaling pathway during neuroprotection leading to phosphorylation of the PI3K/Akt signaling pathways through downregulation of PTEN. In contrast, cotreatment of GH with the Notch signaling inhibitor, DAPT, prevented its neuroprotective effect against KA. We identified binding sites in Notch1 and Notch2 genes for STAT5. Also, GH prevented Müller cell transdifferentiation and downregulated Sox2, FGF2, and PCNA after cotreatment with KA. Additionally, GH modified TNF receptors immunoreactivity suggesting anti-inflammatory actions. CONCLUSIONS. Our data indicate that the neuroprotective effects of GH against KA injury in the retina are mediated through the regulation of Notch signaling. Additionally, anti-inflammatory and antiproliferative effects were observed.

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“…It is well known that there are two different steps of GH action: at first, GH is directly mediated by GHR to be transducted to IGF1; and then the IGF-1 acts on target cells to exert the physiological effect of GH [ 4 , 81 ]. Although GH acts in nearly every tissue of the body, the most known for its growth promoting effect of GH is on cartilage and bone, especially during the adolescent years.…”

Section: Discussionmentioning

confidence: 99%

“…Growth hormone (GH), also known as somatotropin, is a peptide hormone released from the anterior pituitary somatotroph cells. GH is involved in the promotion of growth, cell division and regeneration [ 1 , 2 ], the regulation of metabolism, immune, reproductive, and cardiovascular systems, and the brain [ 3 , 4 ]. GH effects are directly mediated through the GH receptor (GHR) and indirectly via insulin-like growth factor 1 (IGF-1).…”

Section: Introductionmentioning

confidence: 99%

Growth Hormone Receptor Mutations Related to Individual Dwarfism

Lin

et al. 2018

IJMS

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Growth hormone (GH) promotes body growth by binding with two GH receptors (GHRs) at the cell surface. GHRs interact with Janus kinase, signal transducers, and transcription activators to stimulate metabolic effects and insulin-like growth factor (IGF) synthesis. However, process dysfunctions in the GH–GHR–IGF-1 axis cause animal dwarfism. If, during the GH process, GHR is not successfully recognized and/or bound, or GHR fails to transmit the GH signal to IGF-1, the GH dysfunction occurs. The goal of this review was to focus on the GHR mutations that lead to failures in the GH–GHR–IGF-1 signal transaction process in the dwarf phenotype. Until now, more than 90 GHR mutations relevant to human short stature (Laron syndrome and idiopathic short stature), including deletions, missense, nonsense, frameshift, and splice site mutations, and four GHR defects associated with chicken dwarfism, have been described. Among the 93 identified mutations of human GHR, 68 occur extracellularly, 13 occur in GHR introns, 10 occur intracellularly, and two occur in the transmembrane. These mutations interfere with the interaction between GH and GHRs, GHR dimerization, downstream signaling, and the expression of GHR. These mutations cause aberrant functioning in the GH-GHR-IGF-1 axis, resulting in defects in the number and diameter of muscle fibers as well as bone development.

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Growth Hormone (GH) and Gonadotropin-Releasing Hormone (GnRH) in the Central Nervous System: A Potential Neurological Combinatory Therapy?

Cited by 43 publications

References 193 publications

The Role of Endogenous Neuroprotective Mechanisms in the Prevention of Retinal Ganglion Cells Degeneration

The Role of Endogenous Neuroprotective Mechanisms in the Prevention of Retinal Ganglion Cells Degeneration

Growth Hormone Neuroprotection Against Kainate Excitotoxicity in the Retina is Mediated by Notch/PTEN/Akt Signaling

Growth Hormone Receptor Mutations Related to Individual Dwarfism

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