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(Reference retrieved automatically from Web of Science through information on FAPESP grant and its corresponding number as mentioned in the publication by the authors.)

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

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Author(s):
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
Total Authors: 9
Affiliation:
[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
Total Affiliations: 4
Document type: Journal article
Source: Neuroscience; v. 434, p. 136-147, MAY 10 2020.
Web of Science Citations: 0
Abstract

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)

FAPESP's process: 16/20897-3 - Role of orexin neurons as mediators of the central effects induced by growth hormone
Grantee:Frederick Wasinski
Support Opportunities: Scholarships in Brazil - Post-Doctoral
FAPESP's process: 14/11752-6 - Study of leptin functions during intrauterine and childhood stages in mice
Grantee:Angela Maria Ramos Lobo
Support Opportunities: Scholarships in Brazil - Doctorate
FAPESP's process: 17/02983-2 - The role of growth hormone in the brain: relevance for neural functions and in disease
Grantee:Jose Donato Junior
Support Opportunities: Research Projects - Thematic Grants
FAPESP's process: 16/09679-4 - Central effects of growth hormone on energetic metabolism and glicemic control
Grantee:Isadora Clivatti Furigo
Support Opportunities: Scholarships in Brazil - Post-Doctoral