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Rôles Des Peptides Dérivés De La Préproghréline Dans Le Contrôle De La Sécrétion De GH Et Du Comportement Alimentaire

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Rôles Des Peptides Dérivés De La Préproghréline Dans Le Contrôle De La Sécrétion De GH Et Du Comportement Alimentaire R^olesdes peptides d´eriv´esde la pr´eproghr´elinedans le contr^olede la s´ecr´etionde GH et du comportement alimentaire Rim Hassouna To cite this version: Rim Hassouna. R^olesdes peptides d´eriv´esde la pr´eproghr´elinedans le contr^olede la s´ecr´etion de GH et du comportement alimentaire. M´edecinehumaine et pathologie. Universit´eRen´e Descartes - Paris V, 2012. Fran¸cais. <NNT : 2012PA05T045>. <tel-00781915> HAL Id: tel-00781915 https://tel.archives-ouvertes.fr/tel-00781915 Submitted on 28 Jan 2013 HAL is a multi-disciplinary open access L'archive ouverte pluridisciplinaire HAL, est archive for the deposit and dissemination of sci- destin´eeau d´ep^otet `ala diffusion de documents entific research documents, whether they are pub- scientifiques de niveau recherche, publi´esou non, lished or not. The documents may come from ´emanant des ´etablissements d'enseignement et de teaching and research institutions in France or recherche fran¸caisou ´etrangers,des laboratoires abroad, or from public or private research centers. publics ou priv´es. UNIVERSITE PARIS DESCARTES PARIS 5 Ecole Doctorale Gc2ID THESE Pour lobtention du grade de DOCTEUR DE LUNIVERSITE PARIS DESCARTES Spécialité Neurosciences Rôles des peptides dérivés de la préproghréline dans le contrôle de la sécrétion de GH et du comportement alimentaire Soutenue publiquement par : Rim HASSOUNA Le 27 novembre 2012 Devant le jury composé de : Pr. Christophe Magnan, Président Dr. Xavier Bonnefont, Rapporteur Dr. Nicolas Chartrel, Rapporteur Dr. Luc Pénicaud, Examinateur Dr. Odile Viltart, Examinateur Dr. Jacques Epelbaum, Directeur de thèse Dr. Virginie Tolle, Directeur de thèse REMERCIEMENTS" " " A"l image"du"générique"final"d un"film,"je"souhaite"exprimer"tous"mes"remerciements" et"ma"reconnaissance"à"tous"les"protagonistes"qui"ont"contribué"à"cette"histoire." " Je"remercie"vivement"tous"les"membres"du"jury"qui"me"font"l honneur"de"juger"cette" thèse":"" M."Xavier"Bonnefont"et"M."Nicolas"Chartrel,"pour"le"temps"qu ils"ont"consacré"à"examiner"et" juger"ce"travail"en"tant"que"rapporteurs,"qu ils"trouvent"ici"l expression"de"toute"ma"gratitude." M."Christophe"Magnan"pour"avoir"accepté"de"présider"le"jury"et"pour"l intérêt"qu il"porte"à"ce" travail." M."Luc"Pénicaud"pour"avoir"accepté"d être"examinateur"de"cette"thèse." Mme"Odile"Viltart"pour"sa"présence"en"tant"qu examinateur"mais"également"pour"toute"son" implication"et"son"intérêt"pour"ce"travail"et""son"extrême"gentillesse."" " Les" travaux" présentés" dans" cette" thèse" ont" été" produits" au" sein" du" Centre" de" Psychiatrie"et"Neurosciences,"dans"l équipe"intitulée"«"Neuroendocrinologie"de"la"croissance" et"de"la"sénescence"»"dirigée"par"M."Jacques"Epelbaum."" Je"souhaite"ainsi"vivement"remercier"Jacques"pour"m avoir"accueillie"au"sein"du"laboratoire" et"offert"l opportunité"de"faire"cette"thèse"également"pour"sa"participation"à"la"direction"de" cette"thèse"et"son"constant"intérêt"pour"mon"travail." " Je"remercie"vivement"et"tout"particulièrement"Mme."Virginie"Tolle"pour"l opportunité" qu elle" m a" offert" d effectuer" ce" travail" au" sein" de" sa" «"petite" équipe"»." Elle" a" dirigé" la" réalisation"de"cette"thèse"avec"toujours"beaucoup"de"patience,"de"douceur"et"de"passion." Travailler"avec"elle"fut"un"réel"plaisir."Qu elle"trouve"ici"l expression"de"mes"remerciements" les"plus"sincères"ainsi"que"de"mon"amitié.""" " Un" grand" merci" à" Philippe" Zizzari," sans" qui" la" majorité" des" expériences" inどvivo" n auraient"pas"été"possibles."Son"expérience"a"été"d une"aide"précieuse"tout"au"long"de"ces" trois"années."Je"lui"adresse"toute"mon"amitié."Je"pense"également"à"Oriane"Fiquet,"travailler" avec"elle"fut"un"réel"plaisir,"je"lui"souhaite"beaucoup"de"réussite"dans"l avenir." " Je" tiens" à" remercier" toute" l équipe," de" sa" configuration" 2009" à" 2012." Tous" ses" membres"ont"ont"eut"un"rôle"à"jouer"aucours""de"cette"thèse":" Jacques" Pantel" pour" les" discussions" scientifiques," les" conseils" et" suggestions" et" pour" tout" l intérêt""qu il"a"porté"à"mon"travail." Catherine" Videau" et" Catherine" Loudes" pour" m avoir" transmis" leur" savoir" et" leur" technicité" notamment"pour"l immunohistochimie"et"les"dosages." " " Emmanuelle" Duron," Dominique" Grouselle," Axelle" Simon," Guillaume" Martel," Emmanuel" Moyse"et"Cécile"Viollet,"pour"nos"discussions"qu elles"soient"scientifiques"ou"non,"pour"leur" conseils"et"leur"sympathie." " Ce"travail"n aurait"pas"pu"avoir"lieu"sans"ses"actrices"et"acteurs"principaux:"les"souris," dont"Alice"et"Chloé"ont"toujours"pris"grand"soin"qu elles"trouvent"ici"l expression"de"toute"ma" reconnaissance." Je" remercie" égalmement" Julie" qui" m a" apporté" son" aide" pour" l expérimentation,"les"journées"de"prélèvement"passaient"vite"en"sa"présence." " Enfin"je"n oublie"pas"ma"famille"et"mes"amis."Mes"parents"qui"m ont"supporté"dans" tous"les"sens"du"terme"et"bien"sûr"Erwan"avec"lequel"j ai"partagé"cette"expérience."Anneど Claude,"AnneどLaure,"Blandine,"Joyce,"Laetitia,"Romain,"Sandra,"Sophie"avec"lesquels"il"a" toujours"été"très"agréable"de"sortir"diner,"aller"au"ciné"ou"tout"simplement"discuter"après" une"bonne"journée"au"labo"!"""" " 3 " La théorie, c'est quand on sait tout et que rien ne fonctionne. La pratique, c'est quand tout fonctionne et que personne ne sait pourquoi. Si la pratique et la théorie sont réunies, rien ne fonctionne et on ne sait pas pourquoi. Albert Einstein. " " " " 6̇̈Ø̋"¸̋œ"Œ̇ßÆÍø̋œ" TABLES"DES"MATIÉRES" " LISTE"DES"FIGURES"ET"TABLEAUX"............................................................................................."6" ABRÉVIATIONS".................................................................................................................................."9" AVANT"PROPOS".............................................................................................................................."11" INTRODUCTION".............................................................................................................................."12" PARTIE"1":"L HORMONE"DE"CROISSANCE"(GH)"...................................................................."14" 1."Structure"et"récepteur"de"la"GH"..........................................................................................."14" 2."Fonctions"de"l hormone"de"croissance".............................................................................."15" " " に┻な┻".̋œ"ƺœ-Øƺ┽ØÆŁ̋"̌øæ¬ß̶"̨̇̊ßæøœ"ゅ+)(ょ"┻┻┻┻┻┻┻┻┻┻┻┻┻┻┻┻┻┻┻┻┻┻┻┻┻┻┻┻┻┻┻┻┻┻┻┻┻┻┻┻┻┻┻┻┻┻┻┻┻┻┻┻┻┻┻┻┻┻┻┻┻┻┻┻┻┻┻┻┻┻┻┻┻┻┻┻┻┻┻┻┻┻┻┻┻┻┻┻┻┻┻┻┻┻┻┻┻┻┻┻┻┻┻┻┻"なは " に┻に┻"4ùØ̋"¸̋"Ø̇")*"¸̇ºœ"Ø̇"̊øæÆœœ̇º̊̋┻┻┻┻┻┻┻┻┻┻┻┻┻┻┻┻┻┻┻┻┻┻┻┻┻┻┻┻┻┻┻┻┻┻┻┻┻┻┻┻┻┻┻┻┻┻┻┻┻┻┻┻┻┻┻┻┻┻┻┻┻┻┻┻┻┻┻┻┻┻┻┻┻┻┻┻┻┻┻┻┻┻┻┻┻┻┻┻┻┻┻┻┻┻┻┻┻┻┻┻┻┻┻┻┻┻┻┻┻┻┻┻┻┻"なは 3."に┻"ぬ┻"4ùØ̋"¸̋"Ø̇")*"¸̇ºœ"Ø̇"øÎ̌-Ø̇ßÆæº"¸-"ŒÎß̇̈æØÆœMode"de"sécrétion"de"la"GH"...................................................Œ̋"κ̋ø̌ÎßÆł-̋"┻┻┻┻┻┻┻┻┻┻┻┻┻┻┻┻┻┻┻┻┻┻┻┻┻┻┻┻┻┻┻┻┻┻┻┻................................................┻┻┻┻┻┻┻┻┻┻┻┻┻┻┻┻┻"なは"17" 4."Régulation"de"la"sécrétion"de"GH"........................................................................................."19" " " ね┻な┻"4Î̌-Ø̇ßÆæº"ı̇ø"Ø̋œ"̨̇̊ß̋-øœ"̊̋ºßø̇-®"┻┻┻┻┻┻┻┻┻4.1.1.1."La"somatolibérine":"GHRH"...................................................┻┻┻┻┻┻┻┻┻┻┻┻┻┻┻┻┻┻┻┻┻┻┻┻┻┻┻┻┻┻┻┻┻┻┻┻┻┻┻┻┻┻┻┻┻┻┻┻┻┻┻...................................................┻┻┻┻┻┻┻┻┻┻┻┻┻┻┻┻┻┻┻┻┻┻┻┻┻┻┻┻┻┻┻┻┻┻┻┻┻┻┻┻┻┻┻┻┻"なひ....."20" ね┻な┻な┻"(̇̊ß̋-øœ"̶°ıæß̶̇Ø̇ŒÆł-̋œ"┻┻┻┻┻┻┻┻┻┻┻┻┻┻┻┻┻┻┻┻┻┻┻┻┻┻┻┻┻┻┻┻┻┻┻┻┻┻┻┻┻┻┻┻┻┻┻┻┻┻┻┻┻┻┻┻┻┻┻┻┻┻┻┻┻┻┻┻┻┻┻┻┻┻┻┻┻┻┻┻┻┻┻┻┻┻┻┻┻┻┻┻┻┻┻┻┻┻┻┻┻┻┻┻┻┻┻┻┻┻┻┻┻┻┻┻┻┻┻┻┻┻┻┻┻┻┻┻┻┻┻┻┻┻┻┻┻"にど 4.1.1.2."La"somatostatine":"SRIH".............................................................................................................."22" 4.1.1.3."Interaction"entre"GHRH"et"SRIH"pour"le"contrôle"de"la"sécrétion"de"GH"....................................."24" 4.1.1.4."Dimorphisme"sexuel"du"mode"de"sécrétion"de"GH"......................................................................"25" 4.1.1.5."Les"autres"facteurs"hypothalamiques"........................................................................................."26" " " ね┻な┻に┻".̋œ"º̋-øæßø̇ºœŒ̋ßß̋-øœ"̶°ıæß̶̇Ø̇ŒÆł-̋œ"æ-"̋®ßø̇┽̶°ıæß̶̇Ø̇ŒÆł-̋œ┻┻┻┻┻┻┻┻┻┻┻┻┻┻┻┻┻┻┻┻┻┻┻┻┻┻┻┻┻┻┻┻┻┻┻┻┻┻┻┻┻┻┻┻┻┻┻┻┻"にぱ " ね┻な┻ぬ"/æ¸ÍØ̋œ"ıæ-ø"Ø╆ƺß̋ø̇̊ßÆæº"̋ºßø̋"Ø̋œ"¸Æ̨̨Îø̋ºßœ"̨̇̊ß̋-øœ"ıæ-ø"øÎ̌-Ø̇ßÆæº"¸̋"Ø̇"œÎ̊øÎßÆæº"¸̋")*"┻"ぬな " ね┻に┻".̋œ"̨̇̊ß̋-øœ"ıÎøÆı̶ÎøÆł-̋œ"┻┻┻┻┻┻┻┻┻┻┻┻┻┻┻┻┻┻┻┻┻┻┻┻┻┻┻┻┻┻┻┻┻┻┻┻┻┻┻┻┻┻┻┻┻┻┻┻┻┻┻┻┻┻┻┻┻┻┻┻┻┻┻┻┻┻┻┻┻┻┻┻┻┻┻┻┻┻┻┻┻┻┻┻┻┻┻┻┻┻┻┻┻┻┻┻┻┻┻┻┻┻┻┻┻┻┻┻┻┻┻┻┻┻┻┻┻┻┻┻┻┻┻┻"ぬな" ね┻に┻な┻".╆ƺœ-Øƺ┽ØÆŁ̋"̌øæ¬ß̶"̨̇̊ßæø"+┺"+)(┽+"┻┻┻┻┻┻┻┻┻┻┻┻┻┻┻┻┻┻┻┻┻┻┻┻┻┻┻┻┻┻┻┻┻┻┻┻┻┻┻┻┻┻┻┻┻┻┻┻┻┻┻┻┻┻┻┻┻┻┻┻┻┻┻┻┻┻┻┻┻┻┻┻┻┻┻┻┻┻┻┻┻┻┻┻┻┻┻┻┻┻┻┻┻┻┻┻┻┻┻┻┻┻┻┻┻┻┻┻┻┻┻┻┻┻┻┻┻┻┻┻"ぬな" ね┻に┻に┻".̋œ"̌Ø-̊æ̊æøßÆ̊æâ¸̋œ"┻┻┻┻┻┻┻┻┻┻┻┻┻┻┻┻┻┻┻┻┻┻┻┻┻┻┻┻┻┻┻┻┻┻┻┻┻┻┻┻┻┻┻┻┻┻┻┻┻┻┻┻┻┻┻┻┻┻┻┻┻┻┻┻┻┻┻┻┻┻┻┻┻┻┻┻┻┻┻┻┻┻┻┻┻┻┻┻┻┻┻┻┻┻┻┻┻┻┻┻┻┻┻┻┻┻┻┻┻┻┻┻┻┻┻┻┻┻┻┻┻┻┻┻┻┻┻┻┻┻┻┻┻┻┻┻┻┻┻┻┻┻┻┻┻┻┻┻┻┻"ぬに" ね┻に┻ぬ┻".̇"Ø̋ıßƺ̋"̋ß"Ø̋œ"œÆ̌º̇-®"ŒÎß̇̈æØÆł-̋œ"̋ß"º-ßøÆßÆ溺̋Øœ"┻┻┻┻┻┻┻┻┻┻┻┻┻┻┻┻┻┻┻┻┻┻┻┻┻┻┻┻┻┻┻┻┻┻┻┻┻┻┻┻┻┻┻┻┻┻┻┻┻┻┻┻┻┻┻┻┻┻┻┻┻┻┻┻┻┻┻┻┻┻┻┻┻┻┻┻┻┻┻┻"ぬに ね┻に┻ね┻".̇")*"┺"øÎßøæ̊æºßøùØ̋"ºÎ̌̇ßÆ̨"┻┻┻┻┻┻┻┻┻┻┻┻┻┻┻┻┻┻┻┻┻┻┻┻┻┻┻┻┻┻┻┻┻┻┻┻┻┻┻┻┻┻┻┻┻┻┻┻┻┻┻┻┻┻┻┻┻┻┻┻┻┻┻┻┻┻┻┻┻┻┻┻┻┻┻┻┻┻┻┻┻┻┻┻┻┻┻┻┻┻┻┻┻┻┻┻┻┻┻┻┻┻┻┻┻┻┻┻┻┻┻┻┻┻┻┻┻┻┻┻┻┻┻┻┻┻┻┻┻┻┻┻┻"ぬぬ PARTIE"2":"LE"COMPORTEMENT"ALIMENTAIRE".................................................................."35" 1."Régulation"de"l homéostasie"énergétique"........................................................................"35" " " な┻な┻"4Î̌-Ø̇ßÆæº"²"̊æ-øß"ß̋øŒ̋"┻┻┻┻┻┻┻┻┻┻┻┻┻┻┻┻┻┻┻┻┻┻┻┻┻┻┻┻┻┻┻┻┻┻┻┻┻┻┻┻┻┻┻┻┻┻┻┻┻┻┻┻┻┻┻┻┻┻┻┻┻┻┻┻┻┻┻┻┻┻┻┻┻┻┻┻┻┻┻┻┻┻┻┻┻┻┻┻┻┻┻┻┻┻┻┻┻┻┻┻┻┻┻┻┻┻┻┻┻┻┻┻┻┻┻┻┻┻┻┻┻┻┻┻┻┻┻┻"ぬの" な┻な┻な┻".̋œ"Œ̇̊øæº-ßøÆŒ̋ºßœ"┻┻┻┻┻┻┻┻┻┻┻┻┻┻┻┻┻┻┻┻┻┻┻┻┻┻┻┻┻┻┻┻┻┻┻┻┻┻┻┻┻┻┻┻┻┻┻┻┻┻┻┻┻┻┻┻┻┻┻┻┻┻┻┻┻┻┻┻┻┻┻┻┻┻┻┻┻┻┻┻┻┻┻┻┻┻┻┻┻┻┻┻┻┻┻┻┻┻┻┻┻┻┻┻┻┻┻┻┻┻┻┻┻┻┻┻┻┻┻┻┻┻┻┻┻┻┻┻┻┻┻┻┻┻┻┻┻┻┻┻┻┻┻┻┻┻┻┻"ぬは"
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