Cited by 643Sexual Differentiation and DisordersEstrogen and related hormone effectsNeuroscience and Neuropharmacology Research

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Understanding the broad influence of sex hormones and sex differences in the brain

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McEwen, Bruce S., Milner, Teresa A.·2017·Journal of Neuroscience Research

DOI 10.1002/jnr.23809PMC PMC5120618

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Abstract

Sex hormones act throughout the entire brain of both males and females via both genomic and nongenomic receptors. Sex hormones can act through many cellular and molecular processes that alter structure and function of neural systems and influence behavior as well as providing neuroprotection. Within neurons, sex hormone receptors are found in nuclei and are also located near membranes, where they are associated with presynaptic terminals, mitochondria, spine apparatus, and postsynaptic densities. Sex hormone receptors also are found in glial cells. Hormonal regulation of a variety of signaling pathways as well as direct and indirect effects on gene expression induce spine synapses, up- or downregulate and alter the distribution of neurotransmitter receptors, and regulate neuropeptide expression and cholinergic and GABAergic activity as well as calcium sequestration and oxidative stress. Many neural and behavioral functions are affected, including mood, cognitive function, blood pressure regulation, motor coordination, pain, and opioid sensitivity. Subtle sex differences exist for many of these functions that are developmentally programmed by hormones and by not yet precisely defined genetic factors, including the mitochondrial genome. These sex differences and responses to sex hormones in brain regions, which influence functions not previously regarded as subject to such differences, indicate that we are entering a new era of our ability to understand and appreciate the diversity of gender-related behaviors and brain functions. © 2016 Wiley Periodicals, Inc.

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Authors: McEwen, B. S., & Milner, T. A.
Affiliations: Rockefeller University (US)
Weill Cornell Medicine (US)
Corresponding author: McEwen, Bruce S.
ORCID: McEwen, Bruce S.
Milner, Teresa A.
Venue: Journal of Neuroscience Research
Publisher: Wiley
Published: 2016-11-07
Volume: 95
Issue: 1-2
Pages: 24-39
ISSN: 0360-4012 (ISSN-L)
1097-4547
DOI: 10.1002/jnr.23809
PMC: PMC5120618
OpenAlex: W2552558587
Cited by: 642
References: 208
Citations by year: 2026: 65 · 2025: 66 · 2024: 71 · 2023: 75 · 2022: 53 · 2021: 61 · 2020: 126 · 2019: 57 · 2018: 37 · 2017: 25 · 2016: 2
FWCI: 3.65
Type: journal article
Language: en
Open access: green
www.ncbi.nlm.nih.gov
Licence: onlinelibrary.wiley.com/termsAndConditions#vor (vor)
Locations: Journal of Neuroscience Research (publishedVersion)
PubMed (publishedVersion)
PubMed Central (acceptedVersion)
Funders: National Institutes of Health (HL098351, DA08259, HL096571, AG016765, MH41256, NS07080)
Topics: Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Sexual Differentiation and Disorders
Life Sciences › Biochemistry, Genetics and Molecular Biology › Endocrinology › Estrogen and related hormone effects
Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
Keywords: sex hormones, sex differences in brain, synaptic plasticity, neurotransmitter receptors, neuropeptide expression, oxidative stress, mood, cognitive function, blood pressure regulation, motor coordination, pain, opioid sensitivity, mitochondrial genome
MeSH terms: Animals, Brain, Female, Humans, Male, Sex Characteristics, Gonadal Steroid Hormones, History, 20th Century, History, 21st Century

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Understanding the broad influence of sex hormones and sex differences in the brain

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