Growth Hormone Receptor Deletion Reduces the Density of Axonal Projections from Hypothalamic Arcuate Nucleus Neurons. (10th May 2020)

• Record Type: Journal Article
• Authors: Wasinski, Frederick; Furigo, Isadora C.; Teixeira, Pryscila D.S.; Ramos-Lobo, Angela M.; Peroni, Cibele N.; Bartolini, Paolo; List, Edward O.; Kopchick, John J.; Donato, Jose
• Is Part Of: Neuroscience. Volume 434(2020)
• Page Start: 136
• Page End: 147
• Publication Date: 2020-05-10
• Subjects: 3V third ventricle -- AgRP agouti-related peptide -- ARH arcuate nucleus of the hypothalamus -- DMH dorsomedial nucleus of the hypothalamus -- GH growth hormone -- GHR growth hormone receptor -- IGF-1 insulin-like growth factor-1 -- IOD integrated optical density -- KO knockout -- LepR leptin receptor -- LHA lateral hypothalamic area -- MC3R melanocortin receptor 3 -- MC4R melanocortin receptor 4 -- NPY neuropeptide Y -- NTS nucleus of the solitary tract -- POMC proopiomelanocortin -- PVH paraventricular nucleus of the hypothalamus -- STAT5 signal transducer and activator of transcription-5 -- WT wild-type; AgRP -- development -- food intake -- GH -- melanocortin system -- POMC; Neurochemistry -- Periodicals; Neurophysiology -- Periodicals; Neurology -- Periodicals; Neurochimie -- Périodiques; Neurophysiologie -- Périodiques; Neurochemistry; Neurophysiology; Electronic journals; Periodicals; Electronic journals; 612.8
• DOI: 10.1016/j.neuroscience.2020.03.037
• Languages: English
• ISSNs: 0306-4522

Abstract

Highlights: Formation of POMC and AgRP projections requires GH and leptin signaling. POMC and AgRP projections are affected by LepR-specific GH receptor disruption. AgRP innervation is impaired in mice carrying AgRP-specific GH receptor ablation. 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.