# The role of dopamine release and D2 dopamine receptor in GHRH and somatostatin cells in controlling growth hormone secretion

**Authors:** Gabriel O. de Souza, Daniela O. Gusmao, Maria E. de Sousa, Marina G. Martins, Alexandre S. Basso, Jose Donato

PMC · DOI: 10.3389/fendo.2025.1741139 · Frontiers in Endocrinology · 2026-01-12

## TL;DR

This study investigates how dopamine and D2 dopamine receptors in specific brain cells affect growth hormone secretion and body composition in mice.

## Contribution

The study reveals that dopamine from GHRH neurons and D2R in GHRH/SST neurons have minor roles in regulating GH and body composition in mice.

## Key findings

- GHRH neurons lacking dopamine production show normal body growth and GH secretion.
- D2R deletion in GHRH or SST neurons slightly affects lean mass and GH in male mice.
- Female mice show no significant differences in GH or body composition with D2R deletion.

## Abstract

Pituitary growth hormone (GH) secretion is primarily controlled by GH-releasing hormone (GHRH) and somatostatin (SST), peptides produced by hypothalamic neurons. Evidence indicates that dopamine also modulates GH secretion, potentially via D2 dopamine receptor (D2R). Additionally, a subset of GHRH neurons in the arcuate nucleus of the hypothalamus expresses tyrosine hydroxylase (TH), the rate-limiting enzyme of dopamine biosynthesis. However, the role of dopamine release from GHRH neurons and the neuronal population that expresses D2R to regulate GH secretion remain currently unknown.

Mice lacking TH specifically in GHRH cells were generated.

GHRHΔTH mice display relatively normal body growth and pulsatile GH secretion compared to control animals. Next, the effects of D2R deletion in GHRH or SST neurons were examined. GHRHΔDrd2 male mice tended to have reduced lean mass and increased adiposity compared to controls, along with decreased basal GH secretion. SSTΔDrd2 male mice also exhibited reduced body weight and lean mass. Total and pulsatile GH secretion, as well as serum insulin-like growth factor 1 (IGF-1) levels, were not different between groups. No significant differences in body growth, GH secretion pattern, and serum IGF-1 concentration were observed among control, GHRHΔDrd2, and SSTΔDrd2 females.

Dopamine production in GHRH neurons is not necessary for regulating body growth or GH secretion. D2R ablation in GHRH or SST neurons has a small impact on lean mass and GH secretion, indicating that these neurons mediate only a minor part of the effects induced by complete D2R absence in male mice.

## Linked entities

- **Genes:** GHRH (growth hormone releasing hormone) [NCBI Gene 2691], SST (somatostatin) [NCBI Gene 6750], DRD2 (dopamine receptor D2) [NCBI Gene 1813], TH (tyrosine hydroxylase) [NCBI Gene 7054]
- **Proteins:** GH1 (growth hormone 1), IGF1 (insulin like growth factor 1)
- **Species:** Mus musculus (taxon 10090)

## Full-text entities

- **Genes:** Ghrh (growth hormone releasing hormone) [NCBI Gene 14601] {aka GRF, Ghrf}, Th (tyrosine hydroxylase) [NCBI Gene 21823], Sst (somatostatin) [NCBI Gene 20604] {aka SOM, SRIF, SS, Smst}, Gh (growth hormone) [NCBI Gene 14599] {aka Gh1, Ghb1}, Drd2 (dopamine receptor D2) [NCBI Gene 13489] {aka D2R, Drd-2}, Igf1 (insulin-like growth factor 1) [NCBI Gene 16000] {aka C730016P09Rik, Igf-1, Igf-I}
- **Diseases:** mass (MESH:C536030), adiposity (MESH:D018205)
- **Chemicals:** Dopamine (MESH:D004298)
- **Species:** Mus musculus (house mouse, species) [taxon 10090]

## Full text

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## Figures

6 figures with captions in the complete paper: https://tomesphere.com/paper/PMC12832554/full.md

## References

48 references — full list in the complete paper: https://tomesphere.com/paper/PMC12832554/full.md

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Source: https://tomesphere.com/paper/PMC12832554