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Aspects biologiques, moléculaires et cliniques de l’axe GH/IGF-I pp 119–142Cite as

La nutrition lors de la période postnatale précoce détermine la fonction somatotrope chez la souris

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Résumé

Selon un nombre croissant de données, plusieurs pathologies humaines auraient une origine développementale, en particulier les carences nutritionnelles intrautérines ou postnatales : les modifications nutritionnelles se traduisent en effet rapidement par des altérations de la croissance somatique. Toutefois, alors qu’un retard de croissance intra-utérin (RCIU) est souvent corrigé après la naissance, la récupération est limitée en cas de restriction alimentaire pendant la période suivant immédiatement la naissance. Nous souhaitions donc déterminer si la nutrition (sous-nutrition ou suralimentation) en postnatal immédiate modifiait ou non la plasticité de la croissance par le biais d’un contrôle développemental de l’axe hormonal somatotrope. Nous avons redistribué des portées de souris pour induire des modifications de la nutrition au cours des premiers jours de vie, et étudié la régulation endocrine de la croissance et le développement de phénotypes de maladies spécifiques chez les souris adultes. Nous avons démontré que la sous-alimentation pendant la période postnatale immédiate retarde la croissance, alors que la suralimentation l’accélère. Dans les deux cas, l’altération de la taille finale a été permanente. Nous avons observé des altérations coordonnées de la GH hypophysaire, du taux d’IGF-I et d’ALS, ainsi que de l’expression du gène de la GH-RH (ou somatolibérine) hypothalamique pendant le développement postnatal. Ces modifications concordaient avec les phénotypes observés. Les altérations de l’axe somatotrope ont persisté à l’âge adulte. Bien que limitées à la période postnatale immédiate, la sous-alimentation et la suralimentation ont entraîné par la suite une réduction de la tolérance au glucose. Ces anomalies métaboliques correspondaient à une sécrétion insuffi sante d’insuline chez les souris sous-alimentées et à une résistance à l’insuline chez les souris suralimentées. En outre, une augmentation de la pression artérielle suggérant une détérioration vasculaire a été observée dans les deux groupes de souris (sous-alimentées et suralimentées). Nos observations indiquent qu’il existe un lien signifi catif entre le régime nutritionnel immédiatement postnatal, le développement somatotrope et certaines pathologies d’apparition tardive chez la souris. Nous suggérons que l’IGF-I, ainsi que le font d’autres hormones comme la leptine, pourrait jouer un rôle en modulant la stimulation hypothalamique de la fonction somatotrope pendant son développement.

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Authors
  1. L. Kappeler
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  2. C. De Magalhaes Filho
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  3. P. Leneuve
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  4. J. Xu
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  5. N. Brunel
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  6. C. Chatziantoniou
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  7. Y. Le Bouc
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  8. M. Holzenberger
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Editor information

Editors and Affiliations

  1. Service d’Explorations Fonctionnelles Endocriniennes, Hôpital d’enfants Armand-Trousseau, 26, avenue du Docteur-Arnold-Netter, 75012, Paris, France

    Yves Le Bouc

  2. Unité Inserm, UPMC, UMRS 938, France

    Yves Le Bouc

  3. Unité d’endocrinologie, maladie osseuse, génétique et gynécologie médicale, Hôpital des Enfants, 330, avenue de Grande-Bretagne TSA 70054, 31059, Toulouse, France

    Maithé Tauber

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Kappeler, L. et al. (2012). La nutrition lors de la période postnatale précoce détermine la fonction somatotrope chez la souris. In: Le Bouc, Y., Tauber, M. (eds) Aspects biologiques, moléculaires et cliniques de l’axe GH/IGF-I. Springer, Paris. https://doi.org/10.1007/978-2-8178-0196-4_11

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  • DOI: https://doi.org/10.1007/978-2-8178-0196-4_11

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