The Pattern of GH Action in the Mouse Brain

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Menezes, Filipe ; Wasinski, Frederick ; de Souza, Gabriel O. ; Nunes, Amanda P. ; Bernardes, Emerson S. ; dos Santos, Sofia N. ; da Silva, Fabio F. A. ; Peroni, Cibele N. ; Oliveira, Joao E. ; Kopchick, John J. ; Brown, Rosemary S. E. ; Fernandez, Gimena ; De Francesco, Pablo N. ; Perello, Mario ; Soares, Carlos R. J. ; Donato Jr, Jose

• Document type: Journal article
• Source: Endocrinology; v. 165, n. 7, p. 16-pg., 2024-05-27.

Abstract

GH acts in numerous organs expressing the GH receptor (GHR), including the brain. However, the mechanisms behind the brain's permeability to GH and how this hormone accesses different brain regions remain unclear. It is well-known that an acute GH administration induces phosphorylation of the signal transducer and activator of transcription 5 (pSTAT5) in the mouse brain. Thus, the pattern of pSTAT5 immunoreactive cells was analyzed at different time points after IP or intracerebroventricular GH injections. After a systemic GH injection, the first cells expressing pSTAT5 were those near circumventricular organs, such as arcuate nucleus neurons adjacent to the median eminence. Both systemic and central GH injections induced a medial-to-lateral pattern of pSTAT5 immunoreactivity over time because GH-responsive cells were initially observed in periventricular areas and were progressively detected in lateral brain structures. Very few choroid plexus cells exhibited GH-induced pSTAT5. Additionally, Ghr mRNA was poorly expressed in the mouse choroid plexus. In contrast, some tanycytes lining the floor of the third ventricle expressed Ghr mRNA and exhibited GH-induced pSTAT5. The transport of radiolabeled GH into the hypothalamus did not differ between wild-type and dwarf Ghr knockout mice, indicating that GH transport into the mouse brain is GHR independent. Also, single-photon emission computed tomography confirmed that radiolabeled GH rapidly reaches the ventral part of the tuberal hypothalamus. In conclusion, our study provides novel and valuable information about the pattern and mechanisms behind GH transport into the mouse brain. (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: 20/10435-8 - Synthesis of recombinant human chorionic gonadotrophine in CHO and HEK-293 cells, purification and physicochemical characterization
• Grantee: Carlos Roberto Jorge Soares
• Support Opportunities: Regular Research Grants
• FAPESP's process: 20/01318-8 - Central nervous system as a target of growth hormone for the regulation of multiple biological functions
• Grantee: Jose Donato Junior
• Support Opportunities: Research Projects - Thematic Grants