Ghrelin Action in the PVH of Male Mice: Accessibility, Neuronal Targets, and CRH Neurons Activation - Institut des Biomolécules Max Mousseron Accéder directement au contenu
Article Dans Une Revue Endocrinology Année : 2023

Ghrelin Action in the PVH of Male Mice: Accessibility, Neuronal Targets, and CRH Neurons Activation

Victor J Duque
Nilufer Sayar
Rodrigo Rorato
Deniz Atasoy
André S Mecawi

Résumé

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.
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Dates et versions

hal-04604426 , version 1 (19-06-2024)

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Gimena Fernandez, Pablo N de Francesco, María P Cornejo, Agustina Cabral, Julieta P Aguggia, et al.. Ghrelin Action in the PVH of Male Mice: Accessibility, Neuronal Targets, and CRH Neurons Activation. Endocrinology, 2023, 164 (11), pp.bqad154. ⟨10.1210/endocr/bqad154⟩. ⟨hal-04604426⟩
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