Ghrelin and obestatin modulate growth hormone‐releasing hormone release and synaptic inputs onto growth hormone‐releasing hormone neurons
Identifieur interne : 006425 ( Main/Exploration ); précédent : 006424; suivant : 006426Ghrelin and obestatin modulate growth hormone‐releasing hormone release and synaptic inputs onto growth hormone‐releasing hormone neurons
Auteurs : Dan D. Feng [France, République populaire de Chine] ; Seung-Kwon Yang [France] ; Catherine Loudes [France] ; Axelle Simon [France] ; Tamara Al-Sarraf [France] ; Michael Culler [États-Unis] ; Rodrigo Alvear-Perez [France] ; Catherine Llorens-Cortes [France] ; Chen Chen [Australie] ; Jacques Epelbaum [France] ; Robert Gardette [France]Source :
- European Journal of Neuroscience [ 0953-816X ] ; 2011-09.
English descriptors
- KwdEn :
- Arcuate, Arcuate nucleus, Basal, Bicu, Bicuculline, Blackwell publishing, Egfp, Endocrinology, Epelbaum, European journal, European neuroscience societies, Explants, Feng, Food intake, Gaba, Gabaergic, Gabaergic synaptic, Gabaergic synaptic responses, Ghrelin, Ghrelin effects, Ghrelin perfusion, Ghrh, Ghrh control, Ghrh neurons, Ghrh release, Ghrl, Glutamate, Glutamatergic, Growth hormone, Growth hormone release, Growth hormone secretagogue receptor, Horvath, Hypothalamic explants, Inserm, Interevent, Mipscs, Neuron, Neuronal, Neurosci, Neuroscience, Obestatin, Obestatin interactions, Peptide, Perfusion, Postsynaptic, Receptor, Ring rate, Scale bars, Secretagogue, Spontaneous action potentials, Srif, Srif release, Synaptic, Time plot, Uorescent, Uorescent protein.
- Teeft :
- Arcuate, Arcuate nucleus, Basal, Bicu, Bicuculline, Blackwell publishing, Egfp, Endocrinology, Epelbaum, European journal, European neuroscience societies, Explants, Feng, Food intake, Gaba, Gabaergic, Gabaergic synaptic, Gabaergic synaptic responses, Ghrelin, Ghrelin effects, Ghrelin perfusion, Ghrh, Ghrh control, Ghrh neurons, Ghrh release, Ghrl, Glutamate, Glutamatergic, Growth hormone, Growth hormone release, Growth hormone secretagogue receptor, Horvath, Hypothalamic explants, Inserm, Interevent, Mipscs, Neuron, Neuronal, Neurosci, Neuroscience, Obestatin, Obestatin interactions, Peptide, Perfusion, Postsynaptic, Receptor, Ring rate, Scale bars, Secretagogue, Spontaneous action potentials, Srif, Srif release, Synaptic, Time plot, Uorescent, Uorescent protein.
Abstract
Ghrelin, a natural ligand of the growth hormone secretagogue receptor (GHS‐R), is synthesized in the stomach but may also be expressed in lesser quantity in the hypothalamus where the GHS‐R is located on growth hormone‐releasing hormone (GHRH) neurons. Obestatin, a peptide derived from the same precursor as ghrelin, is able to antagonize the ghrelin‐induced increase of growth hormone (GH) secretion in vivo but not from pituitary explants in vitro. Thus, the blockade of ghrelin‐induced GH release by obestatin could be mediated at the hypothalamic level by the neuronal network that controls pituitary GH secretion. Ghrelin increased GHRH and decreased somatostatin (somatotropin‐releasing inhibitory factor) release from hypothalamic explants, whereas obestatin only reduced the ghrelin‐induced increase of GHRH release, thus indicating that the effect of ghrelin and obestatin is targeted to GHRH neurons. Patch‐clamp recordings on mouse GHRH‐enhanced green fluorescent protein neurons indicated that ghrelin and obestatin had no significant effects on glutamatergic synaptic transmission. Ghrelin decreased GABAergic synaptic transmission in 44% of the recorded neurons, an effect blocked in the presence of the GHS‐R antagonist BIM28163, and stimulated the firing rate of 78% of GHRH neurons. Obestatin blocked the effects of ghrelin by acting on a receptor different from the GHS‐R. These data suggest that: (i) ghrelin increases GHRH neuron excitability by increasing their action potential firing rate and decreasing the strength of GABA inhibitory inputs, thereby leading to an enhanced GHRH release; and (ii) obestatin counteracts ghrelin actions. Such interactions on GHRH neurons probably participate in the control of GH secretion.
Url:
DOI: 10.1111/j.1460-9568.2011.07787.x
Affiliations:
- Australie, France, République populaire de Chine, États-Unis
- Massachusetts, Île-de-France
- Paris
- Université Paris-Descartes
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wicri:level="4"><country xml:lang="fr">France</country><wicri:regionArea>Faculté de Médecine, Université Paris Descartes, Sorbonne Paris Cité, Paris</wicri:regionArea><placeName><region type="region">Île-de-France</region><region type="old region">Île-de-France</region><settlement type="city">Paris</settlement><settlement type="city">Paris</settlement></placeName><orgName type="university">Université Paris-Descartes</orgName></affiliation></author></analytic><monogr></monogr><series><title level="j" type="main">European Journal of Neuroscience</title><title level="j" type="alt">EUROPEAN JOURNAL OF NEUROSCIENCE</title><idno type="ISSN">0953-816X</idno><idno type="eISSN">1460-9568</idno><imprint><biblScope unit="vol">34</biblScope><biblScope unit="issue">5</biblScope><biblScope unit="page" from="732">732</biblScope><biblScope unit="page" to="744">744</biblScope><biblScope unit="page-count">13</biblScope><publisher>Blackwell Publishing Ltd</publisher><pubPlace>Oxford, UK</pubPlace><date type="published" when="2011-09">2011-09</date></imprint><idno type="ISSN">0953-816X</idno></series></biblStruct></sourceDesc><seriesStmt><idno type="ISSN">0953-816X</idno></seriesStmt></fileDesc><profileDesc><textClass><keywords scheme="KwdEn" xml:lang="en"><term>Arcuate</term><term>Arcuate nucleus</term><term>Basal</term><term>Bicu</term><term>Bicuculline</term><term>Blackwell publishing</term><term>Egfp</term><term>Endocrinology</term><term>Epelbaum</term><term>European journal</term><term>European neuroscience societies</term><term>Explants</term><term>Feng</term><term>Food intake</term><term>Gaba</term><term>Gabaergic</term><term>Gabaergic synaptic</term><term>Gabaergic synaptic responses</term><term>Ghrelin</term><term>Ghrelin effects</term><term>Ghrelin perfusion</term><term>Ghrh</term><term>Ghrh control</term><term>Ghrh neurons</term><term>Ghrh release</term><term>Ghrl</term><term>Glutamate</term><term>Glutamatergic</term><term>Growth hormone</term><term>Growth hormone release</term><term>Growth hormone secretagogue receptor</term><term>Horvath</term><term>Hypothalamic explants</term><term>Inserm</term><term>Interevent</term><term>Mipscs</term><term>Neuron</term><term>Neuronal</term><term>Neurosci</term><term>Neuroscience</term><term>Obestatin</term><term>Obestatin interactions</term><term>Peptide</term><term>Perfusion</term><term>Postsynaptic</term><term>Receptor</term><term>Ring rate</term><term>Scale bars</term><term>Secretagogue</term><term>Spontaneous action potentials</term><term>Srif</term><term>Srif release</term><term>Synaptic</term><term>Time plot</term><term>Uorescent</term><term>Uorescent protein</term></keywords><keywords scheme="Teeft" xml:lang="en"><term>Arcuate</term><term>Arcuate nucleus</term><term>Basal</term><term>Bicu</term><term>Bicuculline</term><term>Blackwell publishing</term><term>Egfp</term><term>Endocrinology</term><term>Epelbaum</term><term>European journal</term><term>European neuroscience societies</term><term>Explants</term><term>Feng</term><term>Food intake</term><term>Gaba</term><term>Gabaergic</term><term>Gabaergic synaptic</term><term>Gabaergic synaptic responses</term><term>Ghrelin</term><term>Ghrelin effects</term><term>Ghrelin perfusion</term><term>Ghrh</term><term>Ghrh control</term><term>Ghrh neurons</term><term>Ghrh release</term><term>Ghrl</term><term>Glutamate</term><term>Glutamatergic</term><term>Growth hormone</term><term>Growth hormone release</term><term>Growth hormone secretagogue receptor</term><term>Horvath</term><term>Hypothalamic explants</term><term>Inserm</term><term>Interevent</term><term>Mipscs</term><term>Neuron</term><term>Neuronal</term><term>Neurosci</term><term>Neuroscience</term><term>Obestatin</term><term>Obestatin interactions</term><term>Peptide</term><term>Perfusion</term><term>Postsynaptic</term><term>Receptor</term><term>Ring rate</term><term>Scale bars</term><term>Secretagogue</term><term>Spontaneous action potentials</term><term>Srif</term><term>Srif release</term><term>Synaptic</term><term>Time plot</term><term>Uorescent</term><term>Uorescent protein</term></keywords></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en">Ghrelin, a natural ligand of the growth hormone secretagogue receptor (GHS‐R), is synthesized in the stomach but may also be expressed in lesser quantity in the hypothalamus where the GHS‐R is located on growth hormone‐releasing hormone (GHRH) neurons. Obestatin, a peptide derived from the same precursor as ghrelin, is able to antagonize the ghrelin‐induced increase of growth hormone (GH) secretion in vivo but not from pituitary explants in vitro. Thus, the blockade of ghrelin‐induced GH release by obestatin could be mediated at the hypothalamic level by the neuronal network that controls pituitary GH secretion. Ghrelin increased GHRH and decreased somatostatin (somatotropin‐releasing inhibitory factor) release from hypothalamic explants, whereas obestatin only reduced the ghrelin‐induced increase of GHRH release, thus indicating that the effect of ghrelin and obestatin is targeted to GHRH neurons. Patch‐clamp recordings on mouse GHRH‐enhanced green fluorescent protein neurons indicated that ghrelin and obestatin had no significant effects on glutamatergic synaptic transmission. Ghrelin decreased GABAergic synaptic transmission in 44% of the recorded neurons, an effect blocked in the presence of the GHS‐R antagonist BIM28163, and stimulated the firing rate of 78% of GHRH neurons. Obestatin blocked the effects of ghrelin by acting on a receptor different from the GHS‐R. These data suggest that: (i) ghrelin increases GHRH neuron excitability by increasing their action potential firing rate and decreasing the strength of GABA inhibitory inputs, thereby leading to an enhanced GHRH release; and (ii) obestatin counteracts ghrelin actions. Such interactions on GHRH neurons probably participate in the control of GH secretion.</div></front></TEI><affiliations><list><country><li>Australie</li><li>France</li><li>République populaire de Chine</li><li>États-Unis</li></country><region><li>Massachusetts</li><li>Île-de-France</li></region><settlement><li>Paris</li></settlement><orgName><li>Université Paris-Descartes</li></orgName></list><tree><country name="France"><region name="Île-de-France"><name sortKey="Feng, Dan D" sort="Feng, Dan D" uniqKey="Feng D" first="Dan D." last="Feng">Dan D. Feng</name></region><name sortKey="Al Arraf, Tamara" sort="Al Arraf, Tamara" uniqKey="Al Arraf T" first="Tamara" last="Al-Sarraf">Tamara Al-Sarraf</name><name sortKey="Al Arraf, Tamara" sort="Al Arraf, Tamara" uniqKey="Al Arraf T" first="Tamara" last="Al-Sarraf">Tamara Al-Sarraf</name><name sortKey="Alvear Erez, Rodrigo" sort="Alvear Erez, Rodrigo" uniqKey="Alvear Erez R" first="Rodrigo" last="Alvear-Perez">Rodrigo Alvear-Perez</name><name sortKey="Epelbaum, Jacques" sort="Epelbaum, Jacques" uniqKey="Epelbaum J" first="Jacques" last="Epelbaum">Jacques Epelbaum</name><name sortKey="Epelbaum, Jacques" sort="Epelbaum, Jacques" uniqKey="Epelbaum J" first="Jacques" last="Epelbaum">Jacques Epelbaum</name><name sortKey="Feng, Dan D" sort="Feng, Dan D" uniqKey="Feng D" first="Dan D." last="Feng">Dan D. Feng</name><name sortKey="Gardette, Robert" sort="Gardette, Robert" uniqKey="Gardette R" first="Robert" last="Gardette">Robert Gardette</name><name sortKey="Gardette, Robert" sort="Gardette, Robert" uniqKey="Gardette R" first="Robert" last="Gardette">Robert Gardette</name><name sortKey="Llorens Ortes, Catherine" sort="Llorens Ortes, Catherine" uniqKey="Llorens Ortes C" first="Catherine" last="Llorens-Cortes">Catherine Llorens-Cortes</name><name sortKey="Loudes, Catherine" sort="Loudes, Catherine" uniqKey="Loudes C" first="Catherine" last="Loudes">Catherine Loudes</name><name sortKey="Loudes, Catherine" sort="Loudes, Catherine" uniqKey="Loudes C" first="Catherine" last="Loudes">Catherine Loudes</name><name sortKey="Simon, Axelle" sort="Simon, Axelle" uniqKey="Simon A" first="Axelle" last="Simon">Axelle Simon</name><name sortKey="Simon, Axelle" sort="Simon, Axelle" uniqKey="Simon A" first="Axelle" last="Simon">Axelle Simon</name><name sortKey="Yang, Seung Won" sort="Yang, Seung Won" uniqKey="Yang S" first="Seung-Kwon" last="Yang">Seung-Kwon Yang</name><name sortKey="Yang, Seung Won" sort="Yang, Seung Won" uniqKey="Yang S" first="Seung-Kwon" last="Yang">Seung-Kwon Yang</name></country><country name="République populaire de Chine"><noRegion><name sortKey="Feng, Dan D" sort="Feng, Dan D" uniqKey="Feng D" first="Dan D." last="Feng">Dan D. Feng</name></noRegion></country><country name="États-Unis"><region name="Massachusetts"><name sortKey="Culler, Michael" sort="Culler, Michael" uniqKey="Culler M" first="Michael" last="Culler">Michael Culler</name></region></country><country name="Australie"><noRegion><name sortKey="Chen, Chen" sort="Chen, Chen" uniqKey="Chen C" first="Chen" last="Chen">Chen Chen</name></noRegion></country></tree></affiliations></record>Pour manipuler ce document sous Unix (Dilib)
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