Cited by 158Sexual Differentiation and DisordersGenetic and Clinical Aspects of Sex Determination and Chromosomal AbnormalitiesNeuroendocrine regulation and behavior

Surprising origins of sex differences in the brain

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McCarthy, Margaret M., Pickett, Lindsay A., VanRyzin, Jonathan W., Kight, Katherine E.·2015·Hormones and Behavior

Abstract

This article is part of a Special Issue "SBN 2014". Discerning the biologic origins of neuroanatomical sex differences has been of interest since they were first reported in the late 60's and early 70's. The centrality of gonadal hormone exposure during a developmental critical window cannot be denied but hormones are indirect agents of change, acting to induce gene transcription or modulate membrane bound signaling cascades. Sex differences in the brain include regional volume differences due to differential cell death, neuronal and glial genesis, dendritic branching and synaptic patterning. Early emphasis on mechanism therefore focused on neurotransmitters and neural growth factors, but by and large these endpoints failed to explain the origins of neural sex differences. More recently evidence has accumulated in favor of inflammatory mediators and immune cells as principle regulators of brain sexual differentiation and reveal that the establishment of dimorphic circuits is not cell autonomous but instead requires extensive cell-to-cell communication including cells of non-neuronal origin. Despite the multiplicity of cells involved the nature of the sex differences in the neuroanatomical endpoints suggests canalization, a process that explains the robustness of individuals in the face of intrinsic and extrinsic variability. We propose that some neuroanatomical endpoints are canalized to enhance sex differences in the brain by reducing variability within one sex while also preventing the sexes from diverging too greatly. We further propose mechanisms by which such canalization could occur and discuss what relevance this may have to sex differences in behavior.

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Research works printed but not linked: 4

  1. Ball GF Riters LV MacDougall-Shackleton SA Balthazart J 2009 Sex differences in brain and behavior and the neuroendocrine control of the motivation to sing Cambridge, UK Cambridge University Press 320 31
  2. Brager D Sickel MJ McCarthy MM 2000 Developmental sex differences in calbindin-D28K and calretinin immunoreactivity in the neonatal rat hypothalamus J Neurobiol 42 315 22 10645971
  3. Park JJ Baum MJ Paredes RG Tobet SA 1996 Neurogenesis and cell migration into the sexually dimorphic preoptic area/anterior hypothalamus of the fetal ferret Journal of neurobiology 30 315 28 8807525
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Authors
McCarthy, M. M., Pickett, L. A., VanRyzin, J. W., & Kight, K. E.
Affiliations
University of Maryland, Baltimore (US)
Corresponding author
McCarthy, Margaret M.
Venue
Hormones and Behavior
Publisher
Elsevier BV
Published
2015-11
Volume
76
Pages
3-10
ISSN
0018-506X (ISSN-L)
OpenAlex
W2024023566
Cited by
158
References
91
Citations by year
2026: 4 · 2025: 7 · 2024: 13 · 2023: 11 · 2022: 7 · 2021: 26 · 2020: 14 · 2019: 18 · 2018: 17 · 2017: 16 · 2016: 23 · 2015: 2
FWCI
8.39
Type
journal article
Language
en
Open access
Locations
  • Hormones and Behavior (publishedVersion)
  • PubMed (publishedVersion)
  • Europe PMC (PubMed Central) (acceptedVersion)
  • PubMed Central (acceptedVersion)
Funders
MMM (RO1MH52716-018, R01NS050525-08, R01MH091424-02)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Sexual Differentiation and Disorders
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetic and Clinical Aspects of Sex Determination and Chromosomal Abnormalities
  • Social Sciences › Psychology › Social Psychology › Neuroendocrine regulation and behavior
Keywords
sex differences in brain, sexual differentiation of the brain, gonadal hormones, critical developmental window, neuroinflammation, immune cells, canalization, dendritic branching, sex differences in behavior, gene transcription
MeSH terms
Animals, Brain, Humans, Sex Characteristics, Sex Differentiation

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