What this means
Neuroactive gonadal steroids and their metabolites are major regulators of brain development, function and plasticity. Their actions on neurons, astrocytes and microglia have been extensively studied, whereas their contribution to the lifelong regulation of myelin has received less attention.
A plain-English summary is on its way. Until then, this is the start of the authors' own summary.
- Who it was tested in
- Earlier studies
- Kind of research
- A summary of earlier studies
The science
- Original title
- Myelin as an emerging dimenpsysion of neuroendocrine brain plasticity: lifelong neuroactive steroid regulation and sex-specific mechanisms.
- Authors
- Schumacher M, Ghoumari AM
- Journal
- Frontiers in neuroendocrinology
- Published
- Oct 26, 2026
- Study type
- Review
- PMID
- 42933737 ↗
Abstract
Neuroactive gonadal steroids and their metabolites are major regulators of brain development, function and plasticity. Their actions on neurons, astrocytes and microglia have been extensively studied, whereas their contribution to the lifelong regulation of myelin has received less attention. This question has acquired new significance with the recognition that myelin remains dynamic throughout life, undergoing activity- and experience-dependent remodeling and regeneration after injury or disease. Here, we review how progesterone and its neuroactive metabolites, estrogens and androgens regulate developmental myelination and myelin repair, and consider the emerging possibility that they may also influence adaptive myelination and maintenance of established myelin. We examine steroid-sensitive checkpoints of oligodendrocyte lineage progression and emphasize that steroid regulation of myelination extends beyond direct actions on oligodendroglial cells to multicellular interactions involving neurons, astrocytes and microglia. Remyelination provides particularly compelling evidence for such regulation: physiological gonadal steroid signaling can be required for efficient oligodendrocyte-mediated repair, and emerging studies indicate that males and females may recruit partly distinct cellular and molecular pathways to achieve similar regenerative outcomes. We further propose that adaptive myelination represents an overlooked dimension of neuroendocrine brain plasticity, potentially linking the changing steroid environment across the lifespan to experience-dependent remodeling of neural circuits. Integrating developmental, adaptive and regenerative myelination into neuroendocrinology may broaden the relevance of neuroactive steroids from demyelinating diseases to neurodevelopmental, neuropsychiatric and neurodegenerative disorders and provide new opportunities for sex- and endocrine-state-informed therapeutic strategies and biomarkers.
Schumacher M, Ghoumari AM Myelin as an emerging dimenpsysion of neuroendocrine brain plasticity: lifelong neuroactive steroid regulation and sex-specific mechanisms. Frontiers in neuroendocrinology. 2026. doi:10.1016/j.yfrne.2026.101293. PMID: 42933737. https://pubmed.ncbi.nlm.nih.gov/42933737/