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The Pattern of GH Action in the Mouse Brain
Filipe Menezes1, Frederick Wasinski2,3, Gabriel O de Souza2
1Biotechnology Center, Instituto de Pesquisas Energéticas e Nucleares, IPEN-CNEN/SP, São Paulo 05508-000, Brazil.
Endocrinology
|May 10, 2024
Summary
Growth hormone (GH) enters the brain independently of its receptor (GHR). GH-responsive cells show a medial-to-lateral activation pattern after GH administration, revealing brain hormone transport mechanisms.
Area of Science:
- Neuroendocrinology
- Hormone signaling in the central nervous system
Background:
- Growth hormone (GH) exerts effects on various organs, including the brain, through the GH receptor (GHR).
- Mechanisms of GH brain permeability and regional distribution are not fully understood.
- GH administration is known to induce signal transducer and activator of transcription 5 (STAT5) phosphorylation (pSTAT5) in the brain.
Purpose of the Study:
- To investigate the pattern and mechanisms of GH transport and action within the mouse brain.
- To identify brain regions responsive to GH and the temporal dynamics of this response.
- To determine the role of the GH receptor (GHR) in brain GH uptake.
Main Methods:
- Analysis of pSTAT5 immunoreactive cells following systemic (IP) and central (intracerebroventricular) GH injections at various time points.
- Assessment of Ghr mRNA expression in specific brain regions, including the choroid plexus and tanycytes.
- Measurement of radiolabeled GH transport into the hypothalamus in wild-type and Ghr knockout mice.
- Confirmation of GH brain distribution using single-photon emission computed tomography (SPECT).
Main Results:
- GH administration induced pSTAT5 in cells near circumventricular organs, such as arcuate nucleus neurons, and showed a progressive medial-to-lateral pattern.
- GH-responsive cells were initially observed in periventricular areas, extending to lateral brain structures over time.
- GH transport into the hypothalamus was GHR-independent, as demonstrated by similar uptake in wild-type and Ghr knockout mice.
- Tanycytes, but not choroid plexus cells, expressed Ghr mRNA and showed GH-induced pSTAT5.
- SPECT confirmed rapid radiolabeled GH distribution to the ventral tuberal hypothalamus.
Conclusions:
- GH brain entry is independent of the GH receptor (GHR).
- GH induces a distinct temporal and spatial pattern of activation in the brain, originating from periventricular regions.
- Specific cells like tanycytes may play a role in GH signaling within the brain.
