Journal article
Ghrelin action in the PVH of male mice: accessibility, neuronal targets and CRH neurons activation
Endocrinology (Philadelphia), Vol.164(11), bqad154
11/2023
DOI: 10.1210/endocr/bqad154
PMCID: PMC11491828
PMID: 37823477
Abstract
Abstract The hormone ghrelin displays several well-characterized functions, including some with pharmaceutical interest. The receptor for ghrelin, the growth hormone secretagogue receptor (GHSR), is expressed in the hypothalamic paraventricular nucleus (PVH), a critical hub for the integration of metabolic, neuroendocrine, autonomic and behavioral functions. Here, we performed a neuroanatomical and functional characterization of the neuronal types mediating ghrelin actions in the PVH of male mice. We found that fluorescent-ghrelin mainly labels PVH neurons immunoreactive for nitric oxide synthase 1 (NOS1, which catalyze the production of nitric oxide - NO). Centrally-injected ghrelin increases c-Fos in NOS1 PVH neurons and NOS1 phosphorylation in the PVH. We also found that a high dose of systemically-injected ghrelin increases ghrelin level in the cerebrospinal fluid and in the periventricular PVH, and induces c-Fos in NOS1 PVH neurons. Such high dose of systemically-injected ghrelin activates a subset of NOS1 PVH neurons, which does not express oxytocin, via an arcuate nucleus-independent mechanism. Finally, we found that pharmacological inhibition of NO production fully abrogates ghrelin-induced increase of calcium concentration in corticotropin-releasing hormone neurons of the PVH whereas it partially impairs ghrelin-induced increase of plasma glucocorticoid levels. Thus, plasma ghrelin can directly target a subset of NO-producing neurons of the PVH that is involved in ghrelin-induced activation of the hypothalamic-pituitary-adrenal neuroendocrine axis.
Details
- Title: Subtitle
- Ghrelin action in the PVH of male mice: accessibility, neuronal targets and CRH neurons activation
- Creators
- Gimena Fernandez - Instituto Multidisciplinario de Biología CelularPablo N De Francesco - Instituto Multidisciplinario de Biología CelularMaría P Cornejo - Instituto Multidisciplinario de Biología CelularAgustina Cabral - Instituto Multidisciplinario de Biología CelularJulieta P Aguggia - Instituto Multidisciplinario de Biología CelularVictor J Duque - Universidade Federal de São PauloNilufer Sayar - University of IowaSonia Cantel - Institut des Biomolécules Max MousseronJuan I Burgos - Centro de Investigaciones CardiovascularesJean-Alain FehrentzRodrigo Rorato - Universidade Federal de São PauloDeniz Atasoy - University of IowaAndré S Mecawi - Universidade Federal de São PauloMario Perello - Instituto Multidisciplinario de Biología Celular
- Resource Type
- Journal article
- Publication Details
- Endocrinology (Philadelphia), Vol.164(11), bqad154
- DOI
- 10.1210/endocr/bqad154
- PMID
- 37823477
- PMCID
- PMC11491828
- NLM abbreviation
- Endocrinology
- ISSN
- 1945-7170
- eISSN
- 1945-7170
- Language
- English
- Electronic publication date
- 10/12/2023
- Date published
- 11/2023
- Academic Unit
- Iowa Neuroscience Institute; Fraternal Order of Eagles Diabetes Research Center; Neuroscience and Pharmacology
- Record Identifier
- 9984479555502771
Metrics
11 Record Views