Expression of growth hormone receptor in the human brain (original) (raw)
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Growth Hormone (GH) Action in the Brain Neural Expression of a GH-Response Gene
Journal of Molecular Neuroscience, 2002
The presence of growth hormone (GH) binding sites and GH-receptor (GHR)-immunoreactive proteins in the brain suggests it is a target site for GH action. This could, however, reflect the presence of GH-binding proteins (GHBP) that are not linked to intracellular signal-transduction mechanisms, rather than authentic receptors. The possibility that GH has actions in the brain therefore has been examined by determining an intracellular mediator of GH action.
The Open Endocrinology Journal, 2012
Effects that growth hormone (GH) may exert on brain function have received attention among many researchers over the past two decades. In patients with impaired pituitary production of this hormone replacement therapies have been demonstrated not only to compensate for GH effects in peripheral organs but also to improve several behaviors related to the brain. For instance, available data suggests that subjects treated with GH have experienced significant improvements in concentration, memory, depression, anxiety and fatigue. Also, pituitary-ectomized male rats showing decreased ability in tasks related to learning and memory are seen to improve their performance in these items following GH replacement. The mechanism underlying these beneficial effects of GH has been the subject of studies in many laboratories. An important aspect in this regard is the discovery of specific receptors in various brain regions related to the functional anatomy of several behaviors affected by the hormone. The aim with this article is to review current knowledge on GH receptors in the brain and discuss possible mechanism for the action of the hormone in its ability to affects brain function.
Expression and function of growth hormone in the nervous system: A brief review
General and Comparative Endocrinology, 2014
There is increasing evidence that growth hormone (GH) expression is not confined exclusively to the pituitary somatotrophs as it is synthesized in many extrapituitary locations. The nervous system is one of those extrapituitary sites. In this brief review we summarize data that substantiate the expression, distribution and characterization of neural GH and detail its roles in neural function, including cellular growth, proliferation, differentiation, neuroprotection and survival, as well as its functional roles in behavior, cognition and neurotransmission. Although systemic GH may exert some of these effects, it is increasingly evident that locally expressed neural GH, acting through intracrine, autocrine or paracrine mechanisms, may also be causally involved as a neurotrophic factor.
Growth Hormone & IGF Research, 1998
Growth hormone (GH) differs from other pituitary hormones in that it can affect a wide spectrum of cellular activities in many different tissues. These disparate actions are, however, mediated by a common receptor, suggesting tissue-specific differences in the post-receptor mechanisms and/or tissue sensitivities to GH stimulation may confer specificity. Tissue sensitivity depends upon the abundance of GH receptors (GHRs) and may be modulated by the amplitude and pulsatility of GH secretion. It may also be dependent upon the presence of non-signal transducing GHbinding proteins (GHBPs), which result from the alternate splicing of GHR gene transcripts. Tissue-specific autoregulation of GHRs and GHBPs could, therefore, contribute to differential tissue responsiveness to GH action. The autoregulation of GHR and GHBP gene transcription in novel central (hypothalamus, brainstem, and cortex/neocortex) and peripheral (spleen) tissues was therefore examined in adult, male Sprague-Dawley rats. For comparative purposes, GHR/GHBP gene expression was also examined in the liver, which has traditionally been considered the major GH-target site.
Distribution of growth hormone-responsive cells in the brain of rats and mice
Brain Research, 2021
A growth hormone (GH) injection is able to induce the phosphorylated form of the signal transducer and activator of transcription 5 (pSTAT5) in a large number of cells throughout the mouse brain. The present study had the objective to map the distribution of GH-responsive cells in the brain of rats that received an intracerebroventricular injection of GH and compare it to the pattern found in mice. We observed that rats and mice exhibited a similar distribution of GH-induced pSTAT5 in the majority of areas of the telencephalon, hypothalamus and brainstem. However, rats exhibited a higher density of GH-responsive cells than mice in the horizontal limb of the diagonal band of Broca (HDB), supraoptic and suprachiasmatic nuclei, whereas mice displayed more GH-responsive cells than rats in the hippocampus, lateral hypothalamic area and dorsal motor nucleus of the vagus (DMX). Since both HDB and DMX contain acetylcholine-producing neurons, pSTAT5 was colocalized with choline acetyltransferase in GH-injected animals. We found that 50.0 ± 4.5% of cholinergic neurons in the rat HDB coexpressed GH-induced pSTAT5, whereas very few co-localizations were observed in the mouse HDB. In contrast, rats displayed fewer cholinergic neurons responsive to GH in the DMX at the level of the area postrema. In summary, pSTAT5 can be used as a marker of GH-responsive cells in the rat brain. Although rats and mice exhibit a relatively similar distribution of GH-responsive neurons, some species-specific differences exist, as exemplified for the responsiveness to GH in distinct populations of cholinergic neurons. 2015). GHR expression is found in numerous organs, but the classical biological functions of GH are mediated by the liver, skeletal muscle, bones and adipose tissue. In several tissues, GH stimulates the expression of insulin-like growth factor-1, which acts as an important mediator of GH's actions in the body (List et al., 2014). Thus, either through the direct activation of GHR or indirectly via insulin-like growth factor-1, GH stimulates cell proliferation, tissue growth and protein synthesis. Additionally, GH regulates several metabolic aspects, including insulin sensitivity and fatty acid mobilization/deposition (
Neural Growth Hormone: An Update
Journal of Molecular Neuroscience, 2003
It is now well established that growth hormone (GH) gene expression is not restricted to the pituitary gland and occurs in many extrapituitary tissues, including the central and peripheral nervous systems. Indeed, GH gene expression occurs in the brain prior to its ontogenic appearance in the pituitary gland, and GH may have evolved phylogenetically as a neuropeptide, rather than as an endocrine. Recent studies on the regulation and roles of neural GH in health and disease are the focus of this brief review.
Distribution of growth hormone-responsive cells in the mouse brain
Brain structure & function, 2016
Growth hormone (GH) exerts important biological effects primarily related to growth and metabolism. However, the role of GH signaling in the brain is still elusive. To better understand GH functions in the brain, we mapped the distribution of GH-responsive cells and identified the receptors involved in GH central effects. For this purpose, mice received an acute intraperitoneal challenge with specific ligands of the GH receptor (mouse GH), prolactin receptor (prolactin) or both receptors (human GH), and their brains were subsequently processed immunohistochemically to detect the phosphorylated form of STAT5 (pSTAT5). GH induced pSTAT5 immunoreactivity in neurons, but not in astroglial cells of numerous brain regions, including the cerebral cortex, nucleus accumbens, hippocampus, septum and amygdala. The most prominent populations of GH-responsive neurons were located in hypothalamic areas, including several preoptic divisions, and the supraoptic, paraventricular, suprachiasmatic, pe...
Molecular Brain Research, 1997
Growth hormone release is under tight control by two hypothalamic hormones: growth hormone-releasing hormone and somatostatin. In addition, synthetic growth hormone secretagogues have also been shown to regulate growth hormone release through the growth Ž. hormone secretagogue receptor GHS-R , suggesting the existence of an additional physiological regulator for growth hormone release. To understand the physiological role of the GHS-R in more detail, we mapped the expression of mRNA for the receptor by in situ hybridization and RNase protection assays using rat and human tissues. In the rat brain, the major signals were detected in multiple hypothalamic nuclei as well as in the pituitary gland. Intense signals were also observed in the dentate gyrus of the hippocampal formation. Other brain areas that displayed localized and discrete signals for the receptor include the CA2 and CA3 regions of the hippocampus, the substantia nigra, ventral tegmental area, and dorsal and median raphe nuclei. In resemblance to the results from rat brain, RNase protection assays using human tissues revealed specific signals in pituitary, hypothalamus and hippocampus. Moreover, a weak signal was noted in the pancreas. The demonstration of hypothalamic and pituitary localization of the GHS-R is consistent with its role in regulating growth hormone release. The expression of the receptor in other central and peripheral regions may implicate its involvement in additional as yet undefined physiological functions. q 1997 Elsevier Science B.V.
A role for growth hormone in neurorestoration and neurogenic processes in the brain
The cerebral growth hormone (GH) axis plays an active role following ischemic injury to the brain. Studies have shown that both GH and its receptor are endogenously upregulated in response to ischemic injury and that GH administration post-injury confers significant neuroprotection. Furthermore, there is evidence that GH has trophic effects on neural stem cells (NSCs). However, whether GH can also aid long term recovery and/or have direct effects on neurogenic processes is unclear. Both in vivo and in vitro studies were carried out to address these issues. In vivo studies using the endothelin-1 model of focal ischemic stroke in adult rats demonstrated that a long-term unilateral continuous intracerebroventricular (ICV) infusion of GH is capable of targeting specific areas of active remodelling and neurogenic processes. Immunohistochemistry analyses revealed that ipsilaterally infused GH localised specifically to neuronal and glial progenitor cells within the ipsilateral subventricul...
Endocrinology, 1998
Recent studies suggest that GH may modulate emotion, behavior, or stress response by its direct actions on the brain, and possible expression of the GH gene in the brain has been predicted. In this study we have investigated whether and where the GH gene is expressed in the brain and how it is regulated. Ribonuclease protection assay and 5Ј-rapid amplification of complementary DNA ends-PCR analyses indicated that the GH gene was expressed in rat brain, initiating at the identical transcription start point as that for pituitary GH gene expression. The brain GH messenger RNA was predominantly detected in the lateral hypothalamus (lh) by in situ reverse transcription-PCR analysis. GH gene expression in the brain was significantly enhanced by GH-releasing hormone administration and was rapidly repressed by exposure to restraint stress in the water, whereas the changes in pituitary GH messenger RNA contents in these circumstances were relatively smaller. The results of the present study suggest that the brain GH is predominantly expressed in lh under the control of physiological conditions to play a role in the modulation of brain functions.