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Growth Hormone Receptor Deletion Reduces the Density of Axonal Projections from Hypothalamic Arcuate Nucleus Neurons

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Autor(es):
Wasinski, Frederick [1] ; Furigo, Isadora C. [1] ; Teixeira, Pryscila D. S. [1] ; Ramos-Lobo, Angela M. [1] ; Peroni, Cibele N. [2] ; Bartolini, Paolo [2] ; List, Edward O. [3, 4] ; Kopchick, John J. [3, 4] ; Donato Jr, Jose
Número total de Autores: 9
Afiliação do(s) autor(es):
[1] Univ Sao Paulo, Inst Ciencias Biomed, Dept Fisiol & Biofis, BR-05508000 Sao Paulo, SP - Brazil
[2] CNEN, IPEN, Ctr Biotecnol, BR-05508900 Sao Paulo, SP - Brazil
[3] Ohio Univ, Edison Biotechnol Inst, Athens, OH 45701 - USA
[4] Ohio Univ, Heritage Coll Osteopath Med, Athens, OH 45701 - USA
Número total de Afiliações: 4
Tipo de documento: Artigo Científico
Fonte: Neuroscience; v. 434, p. 136-147, MAY 10 2020.
Citações Web of Science: 0
Resumo

The arcuate nucleus (ARH) is an important hypothalamic area for the homeostatic control of feeding and other metabolic functions. In the ARH, proopiomelanocortin-(POMC) and agouti-related peptide (AgRP)expressing neurons play a key role in the central regulation of metabolism. These neurons are influenced by circulating factors, such as leptin and growth hormone (GH). The objective of the present study was to determine whether a direct action of GH on ARH neurons regulates the density of POMC and AgRP axonal projections to major postsynaptic targets. We studied POMC and AgRP axonal projections to the hypothalamic paraventricular (PVH), lateral (LHA) and dorsomedial (DMH) nuclei in leptin receptor (LepR)-deficient mice (Lepr(db/db)), GH-deficient mice (Ghrhr(lit/lit)) and in mice carrying specific ablations of GH receptor (GHR) either in LepR- or AgRP-expressing cells. Lepr(db/db) mice presented reduction in the density of POMC innervation to the PVH compared to wild-type and Ghrhr(lit/lit) mice. Additionally, both Lepr(db/db) and Ghrhr(lit/lit) mice showed reduced AgRP fiber density in the PVH, LHA and DMH. LepR GHR knockout mice showed decreased density of POMC innervation in the PVH and DMH, compared to control mice, whereas a reduction in the density of AgRP innervation was observed in all areas analyzed. Conversely, AgRP-specific ablation of GHR led to a significant reduction in AgRP projections to the PVH, LHA and DMH, without affecting POMC innervation. Our findings indicate that GH has direct trophic effects on the formation of POMC and AgRP axonal projections and provide additional evidence that GH regulates hypothalamic neurocircuits controlling energy homeostasis. (C) 2020 IBRO. Published by Elsevier Ltd. All rights reserved. (AU)

Processo FAPESP: 16/20897-3 - Papel dos neurônios orexina como mediadores dos efeitos centrais induzidos pelo hormônio do crescimento
Beneficiário:Frederick Wasinski
Linha de fomento: Bolsas no Brasil - Pós-Doutorado
Processo FAPESP: 14/11752-6 - Estudo das funções da leptina durante o período intrauterino e infância no camundongo
Beneficiário:Angela Maria Ramos Lobo
Linha de fomento: Bolsas no Brasil - Doutorado
Processo FAPESP: 17/02983-2 - Ação do hormônio do crescimento no sistema nervoso: relevância para as funções neurais e na doença
Beneficiário:Jose Donato Junior
Linha de fomento: Auxílio à Pesquisa - Temático
Processo FAPESP: 16/09679-4 - Estudo dos efeitos centrais do hormônio do crescimento sobre o metabolismo energético e controle glicêmico
Beneficiário:Isadora Clivatti Furigo
Linha de fomento: Bolsas no Brasil - Pós-Doutorado