title: IGF-1 Induces GHRH Neuronal Axon Elongation during Early Postnatal Life in Mice.
abstract: Nutrition during the perinatal period programs body growth. Growth hormone (GH) secretion from the pituitary regulates body growth and is controlled by Growth Hormone Releasing Hormone (GHRH) neurons located in the arcuate nucleus of the hypothalamus. We observed that dietary restriction during the early postnatal period (i.e. lactation) in mice influences postnatal growth by permanently altering the development of the somatotropic axis in the pituitary gland. This alteration may be due to a lack of GHRH signaling during this critical developmental period. Indeed, underfed pups showed decreased insulin-like growth factor I (IGF-I) plasma levels, which are associated with lower innervation of the median eminence by GHRH axons at 10 days of age relative to normally fed pups. IGF-I preferentially stimulated axon elongation of GHRH neurons in in vitro arcuate explant cultures from 7 day-old normally fed pups. This IGF-I stimulating effect was selective since other arcuate neurons visualized concomitantly by neurofilament labeling, or AgRP immunochemistry, did not significantly respond to IGF-I stimulation. Moreover, GHRH neurons in explants from age-matched underfed pups lost the capacity to respond to IGF-I stimulation. Molecular analyses indicated that nutritional restriction was associated with impaired activation of AKT. These results highlight a role for IGF-I in axon elongation that appears to be cell selective and participates in the complex cellular mechanisms that link underfeeding during the early postnatal period with programming of the growth trajectory.
authors.affiliation: Sorbonne Universités, UPMC Univ Paris 06, INSERM, UMRS 938, Centre de Recherche St-Antoine (CRSA), Paris, France.
authors.forename: Lyvianne
authors.initials: L
authors.lastname: Decourtye
authors.affiliation: Sorbonne Universités, UPMC Univ Paris 06, INSERM, UMRS 938, Centre de Recherche St-Antoine (CRSA), Paris, France.
authors.forename: Erik
authors.initials: E
authors.lastname: Mire
authors.affiliation: Sorbonne Universités, UPMC Univ Paris 06, INSERM, UMRS 938, Centre de Recherche St-Antoine (CRSA), Paris, France.
authors.forename: Maud
authors.initials: M
authors.lastname: Clemessy
authors.affiliation: Sorbonne Universités, UPMC Univ Paris 06, INSERM, UMRS 938, Centre de Recherche St-Antoine (CRSA), Paris, France.
authors.forename: Victor
authors.initials: V
authors.lastname: Heurtier
authors.affiliation: Sorbonne Universités, UPMC Univ Paris 06, INSERM, UMRS 938, Centre de Recherche St-Antoine (CRSA), Paris, France.
authors.forename: Tatiana
authors.initials: T
authors.lastname: Ledent
authors.affiliation: MRC, National Institute for Medical Research, Division of Molecular Neuroendocrinology, London, United Kingdom.
authors.forename: Iain C
authors.initials: IC
authors.lastname: Robinson
authors.affiliation: Universités Montpellier 1 and 2, CNRS, UMR 5203, Institut de Génomique Fonctionnelle, Montpellier, France.
authors.forename: Patrice
authors.initials: P
authors.lastname: Mollard
authors.affiliation: Sorbonne Paris Cité, Université Paris Descartes, INSERM, UMR 894, Centre de Psychiatrie et Neurosciences, Paris, France.
authors.forename: Jacques
authors.initials: J
authors.lastname: Epelbaum
authors.affiliation: McGill University, Douglas Mental Health University Institute, Montreal, Canada.
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Meaney
authors.affiliation: Ecole Normale Supérieure, Institut de Biologie de l'ENS, IBENS, Paris, France.
authors.forename: Sonia
authors.initials: S
authors.lastname: Garel
authors.affiliation: Sorbonne Universités, UPMC Univ Paris 06, INSERM, UMRS 938, Centre de Recherche St-Antoine (CRSA), Paris, France.
authors.forename: Yves
authors.initials: Y
authors.lastname: Le Bouc
authors.affiliation: Sorbonne Universités, UPMC Univ Paris 06, INSERM, UMRS 938, Centre de Recherche St-Antoine (CRSA), Paris, France.
authors.forename: Laurent
authors.initials: L
authors.lastname: Kappeler
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D001369:Axons / Q000187:drug effects* / Q000378:metabolism / Q000502:physiology; D005260:Female; D013007:Growth Hormone-Releasing Hormone / Q000378:metabolism*; D048788:Growth and Development / Q000187:drug effects; D007334:Insulin-Like Growth Factor I / Q000494:pharmacology* / Q000502:physiology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D000071446:Neuronal Outgrowth / Q000187:drug effects*; D009474:Neurons / Q000187:drug effects* / Q000378:metabolism / Q000502:physiology
chemical_list: D007334:Insulin-Like Growth Factor I; D013007:Growth Hormone-Releasing Hormone