Sexual differentiation of the vertebrate brain: principles and mechanisms.
Level 5 - mechanism / opinion, no new human data
Narrative review of animal models and human mechanistic concepts without systematic methodology or primary human trial data.
PubMed 9799588 · doi:10.1006/frne.1998.0171
What was done
This narrative review synthesizes research across vertebrate species, including animal models and humans, on the hormonal, temporal, and cellular mechanisms governing structural sexual dimorphism in the brain.
What was found
The abstract reports no quantitative data. Qualitatively, brain sexual differentiation across vertebrates is driven primarily by gonadal androgens acting during early development, frequently requiring secondary exposure in adulthood for full expression. Mechanistic pathways vary by species: rodents often require aromatization of androgens into estrogens acting on estrogen receptors, whereas other species rely directly on androgen receptor signaling, with little evidence supporting aromatization in primates or humans. Steroids alter distributed neural networks rather than single isolated nuclei through mechanisms including neurogenesis, apoptosis, cell migration, synaptogenesis, synapse elimination, and differentiation. At the time of publication, definitive proof of early steroid-induced brain masculinization in humans was lacking.
Why it matters
The review outlines core principles of neural sexual differentiation across vertebrates and highlights key species differences, warning against direct extrapolation of rodent aromatization pathways to primates and humans.
Limits
As a narrative review, it lacks a systematic search methodology, meta-analytic pooling, and reported sample sizes. Direct experimental evidence establishing causal steroid effects during human development is constrained by ethical and methodological boundaries.
Cited by
- context During fetal development, estrogen plays an essential role in masculinizing regions of the male brain.