# Glucocorticoids and cell fate in the developing brain: Neuroendocrine mechanisms shaping developmental trajectories

**Authors:** Helen Eachus

PMC · DOI: 10.1111/jne.70142 · Journal of Neuroendocrinology · 2026-02-06

## TL;DR

This paper explores how stress hormones like glucocorticoids influence the development of the brain by affecting the fate of neural stem cells.

## Contribution

The paper introduces cell fate as a new perspective to understand how stress hormones shape brain development.

## Key findings

- Glucocorticoids may influence the identities of cells produced during brain development.
- Early life stress could alter developmental trajectories through effects on cell fate.
- Stress hormones act directly on neural stem and progenitor populations.

## Abstract

Early life stress (ELS) is a major risk factor for later psychiatric and neurological disorders. Glucocorticoids (GCs), the hormonal end‐products of the neuroendocrine stress response, are central mediators of this risk, influencing how the developing brain grows and adapts. Research has shown that GCs affect processes such as cell proliferation, neuronal survival, and maturation, but much less attention has been given to whether they also shape cell fate—the developmental choices that determine whether stem and progenitor cells give rise to neurons, astrocytes, oligodendrocytes, or other specialised lineages. In this perspective, I argue that cell fate provides a valuable new lens for understanding how stress becomes embedded in brain architecture. Because GCs act directly on neural stem and progenitor populations, it is plausible that their influence extends beyond the quantity of cells produced, to the identities that emerge. I outline an initial framework for interpreting potential effects of GCs on fate, review emerging evidence from different model systems, and consider mechanisms by which stress hormones could alter developmental trajectories. By focusing on fate, this article highlights a novel dimension of neuroendocrine influence on brain development, with implications for how early experiences confer vulnerability, or resilience, to later mental health outcomes.

## Full-text entities

- **Genes:** NPY (neuropeptide Y) [NCBI Gene 4852] {aka PYY4}, ZBTB16 (zinc finger and BTB domain containing 16) [NCBI Gene 7704] {aka PLZF, ZNF145}, BDNF (brain derived neurotrophic factor) [NCBI Gene 627] {aka ANON2, BULN2}, EOMES (eomesodermin) [NCBI Gene 8320] {aka TBR2}, PBX3 (PBX homeobox 3) [NCBI Gene 5090], AGRP (agouti related neuropeptide) [NCBI Gene 181] {aka AGRT, ART, ASIP2}, CARTPT (CART prepropeptide) [NCBI Gene 9607] {aka CART}, AVP (arginine vasopressin) [NCBI Gene 551] {aka ADH, ARVP, AVP-NPII, AVRP, VP}, Gsr (glutathione-disulfide reductase) [NCBI Gene 116686], CA2 (carbonic anhydrase 2) [NCBI Gene 760] {aka CA-II, CAC, CAII, Car2, HEL-76, HEL-S-282}, HTT (huntingtin) [NCBI Gene 3064] {aka HD, IT15, LOMARS}, TGFB1 (transforming growth factor beta 1) [NCBI Gene 7040] {aka CAEND1, CED, DPD1, IBDIMDE, LAP, TGF-beta1}, Gfap (glial fibrillary acidic protein) [NCBI Gene 14580], PAX6 (paired box 6) [NCBI Gene 5080] {aka AN, AN1, AN2, ASGD5, D11S812E, FVH1}, SOX2 (SRY-box transcription factor 2) [NCBI Gene 6657] {aka ANOP3, MCOPS3}, Th (tyrosine hydroxylase) [NCBI Gene 25085] {aka The}, Chat (choline O-acetyltransferase) [NCBI Gene 290567], CRH (corticotropin releasing hormone) [NCBI Gene 1392] {aka CRF, CRH1}, PMCH (pro-melanin concentrating hormone) [NCBI Gene 5367] {aka MCH, ppMCH}
- **Diseases:** adrenal pheochromocytoma (MESH:D010673), schizophrenia (MESH:D012559), MODULATION (MESH:C538399), abuse (MESH:D019966), depression (MESH:D003866), MEDIATED (MESH:C567355), BRAIN (MESH:D001927), neurological disorders (MESH:D009461), MECHANISMS (MESH:D041781), CELL FATE (OMIM:252500), neuroinflammation (MESH:D000090862), neuropsychiatric symptoms (MESH:D001523), ELS (MESH:D000079225), neurodevelopmental disorders (MESH:D002658), inflammatory (MESH:D007249)
- **Chemicals:** corticosterone (MESH:D003345), dexamethasone (MESH:D003907), cortisol (MESH:D006854)
- **Species:** Homo sapiens (human, species) [taxon 9606], Rattus norvegicus (brown rat, species) [taxon 10116], Rodentia (rodent, order) [taxon 9989], Mus musculus (house mouse, species) [taxon 10090], Danio rerio (leopard danio, species) [taxon 7955]
- **Cell lines:** PC12 — Rattus norvegicus (Rat), Rat adrenal gland pheochromocytoma, Cancer cell line (CVCL_0481)

## Full text

_Full body text omitted from this summary view._ Fetch the complete paper as Markdown: https://tomesphere.com/paper/PMC12879281/full.md

## Figures

1 figure with captions in the complete paper: https://tomesphere.com/paper/PMC12879281/full.md

## References

101 references — full list in the complete paper: https://tomesphere.com/paper/PMC12879281/full.md

---
Source: https://tomesphere.com/paper/PMC12879281