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      Co-Localization of Growth Hormone Secretagogue Receptor and NPY mRNA in the Arcuate Nucleus of the Rat

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          Growth hormone secretagogues (GHS) are small, synthetic compounds which have the potential of releasing growth hormone (GH) from the pituitary. The mechanism of action of GHS has not been fully elucidated. A specific GHS receptor (GHS-R) is expressed in the pituitary gland and in several areas of the brain including the hypothalamus. We have characterized the GHS-R-mRNA-expressing neurons with respect to co-expression of selected neurotransmitters in the hypothalamus. This was done by dual chromogenic and autoradiographic in situ hybridization with riboprobes for GHS-R mRNA and neuropeptide Y (NPY), pro-opiomelanocortin (POMC), somatostatin (SRIH) or GH-releasing hormone (GHRH) mRNA. In the arcuate nucleus, GHS-R mRNA was expressed in 94 ± 1% of the neurons expressing NPY, 8 ± 2% of those expressing POMC and 30 ± 6% expressing SRIH mRNA. 20–25% of the GHRH- mRNA-expressing neurons contained GHS-R mRNA, whereas the vast majority of the arcuate GHS-R-mRNA-containing cells did not contain GHRH mRNA. The finding of a significant co-expression of GHS-R and NPY mRNA in the arcuate nucleus is in accordance with the previous demonstration by Dickson et al. that c-Fos is induced in NPY neurons following GHS administration. These results indicate that GHS have other effects on neuroendocrine regulation than GH release via GHRH neurons. Stimulation of the arcuate NPY neurons via GHS-R may explain the increased appetite and the cortisol release seen after administration of some GHS compounds.

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          Most cited references 6

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          Distribution of mRNA encoding the growth hormone secretagogue receptor in brain and peripheral tissues

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            An arcuato-paraventricular and -dorsomedial hypothalamic neuropeptide Y-containing system which lacks noradrenaline in the rat.

            The origins of neuropeptide Y-like immunoreactive (NPYI) fibers in the paraventricular and dorsomedial hypothalamic nuclei of the rat were examined using immunohistochemistry. Destruction of the arcuate nucleus resulted in a marked decrease of NPYI fibers ipsilaterally in these nuclei, suggesting that most of NPYI fibers in these nuclei originate from NPYI neurons in the arcuate nucleus. These NPYI systems did not contain noradrenalin.
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              Systemic administration of growth hormone-releasing peptide activates hypothalamic arcuate neurons.

              The synthetic hexapeptide growth hormone-releasing peptide selectively releases growth hormone in many species including man. Growth hormone-releasing peptide directly stimulates growth hormone release by an action at the level of the pituitary, at a different receptor site to that for the endogenous 44-amino acid peptide, growth hormone-releasing hormone, and when administered with growth hormone-releasing hormone has a synergistic effect. In addition to this pituitary action, we have suggested that the potent in vivo growth hormone-releasing activity of growth hormone-releasing peptide reflects a hypothalamic action and growth hormone-releasing peptide binding sites have been reported to be present in the hypothalamus. We have now found more direct evidence for a hypothalamic action of growth hormone-releasing peptide in two ways. First, we have found that a sub-population of hypothalamic neurons show strongly increased fos expression in response to systemic growth hormone-releasing peptide administration. Fos is the protein product of the immediate early gene, c-fos, which is induced in many neuronal systems following their activation. Second, extracellular recordings from putative growth hormone-releasing hormone neurons in the arcuate nucleus showed that growth hormone-releasing peptide also stimulates the firing of neurons in this area.

                Author and article information

                S. Karger AG
                November 1999
                17 November 1999
                : 70
                : 5
                : 306-316
                Department of Histology, Health Care Pharmacology, Health Care Discovery, Novo Nordisk A/S, Bagsværd, Denmark
                54491 Neuroendocrinology 1999;70:306–316
                © 1999 S. Karger AG, Basel

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                Page count
                Figures: 4, Tables: 1, References: 40, Pages: 11
                Functional Neuroanatomy of Hypothalamic Neurons


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