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

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Fernandez, Gimena ; De Francesco, Pablo N. ; Cornejo, Maria P. ; Cabral, Agustina ; Aguggia, Julieta P. ; Duque, Victor J. ; Sayar, Nilufer ; Cantel, Sonia ; Burgos, Juan, I ; Fehrentz, Jean-Alain ; Rorato, Rodrigo ; Atasoy, Deniz ; Mecawi, Andre S. ; Perello, Mario

• Tipo de documento: Artigo Científico
• Fonte: Endocrinology; v. 164, n. 11, p. 15-pg., 2023-09-23.

Resumo

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 the ghrelin level in the cerebrospinal fluid and in the periventricular PVH, and induces c-Fos in NOS1 PVH neurons. Such a high dose of systemically injected ghrelin activates a subset of NOS1 PVH neurons, which do 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. (AU)

• Processo FAPESP: 16/17968-6 - Circuitaria e fenótipos neuronais hipotalâmicos envolvidos no acoplamento da atividade do eixo hipotálamo-hipófise-adrenal às alterações da homeostase energética
• Beneficiário: Rodrigo César Rorato
• Modalidade de apoio: Auxílio à Pesquisa - Jovens Pesquisadores
• Processo FAPESP: 19/27581-0 - Controle da secreção de vasopressina na gestação e suas implicações na fisiopatologia da Pré-Eclâmpsia
• Beneficiário: Andre de Souza Mecawi
• Modalidade de apoio: Auxílio à Pesquisa - Jovens Pesquisadores