Cited by 160Stress Responses and CortisolNeuropeptides and Animal PhysiologyNeurotransmitter Receptor Influence on Behavior

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Sex Differences in Molecular and Cellular Substrates of Stress

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Bangasser, Debra A., Valentino, Rita J.·2012·Cellular and Molecular Neurobiology

DOI 10.1007/s10571-012-9824-4PMC PMC3378920

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Abstract

Women are twice as likely as men to suffer from stress-related psychiatric disorders, like unipolar depression and post-traumatic stress disorder. Although the underlying neural mechanisms are not well characterized, the pivotal role of stress in the onset and severity of these diseases has led to the idea that sex differences in stress responses account for this sex bias. Corticotropin-releasing factor (CRF) orchestrates stress responses by acting both as a neurohormone to initiate the hypothalamic-pituitary-adrenal (HPA) axis and as a neuromodulator in the brain. One target of CRF modulation is the locus coeruleus (LC)-norepinephrine system, which coordinates arousal components of the stress response. Hypersecretion of CRF and dysregulation of targets downstream from CRF, such as the HPA axis and LC-norepinephrine system, are characteristic features of many stress-related psychiatric diseases, suggesting a causal role for CRF and its targets in the development of these disorders. This review will describe sex differences in CRF and the LC-norepinephrine system that can increase stress sensitivity in females, making them vulnerable to stress-related disorders. Evidence for gonadal hormone regulation of hypothalamic CRF is discussed as an effect that can lead to increased HPA axis activity in females. Sex differences in the structure of LC neurons that create the potential for hyperarousal in response to emotional stimuli are described. Finally, sex differences at the molecular level of the CRF(1) receptor that make the LC-norepinephrine system more reactive in females are reviewed. The implications of these sex differences for the treatment of stress-related psychiatric disorders also will be discussed.

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Valentino RJ, Van Bockstaele E (2005) Functional interactions between stress neuromediator and the locus coeruleur–noradrenaline system. In: Steckler TK (ed) Handbook of stress and the brain. Elsevier, Amsterdam, pp 465–486

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Authors: Bangasser, D. A., & Valentino, R. J.
Affiliations: Children's Hospital of Philadelphia (US)
Corresponding author: Valentino, Rita J.
ORCID: Bangasser, Debra A.
Valentino, Rita J.
Venue: Cellular and Molecular Neurobiology
Publisher: Springer Science and Business Media LLC
Published: 2012-04-10
Volume: 32
Issue: 5
Pages: 709-723
ISSN: 0272-4340 (ISSN-L)
1573-6830
DOI: 10.1007/s10571-012-9824-4
PMC: PMC3378920
OpenAlex: W2067632849
Cited by: 160
References: 181
Citations by year: 2026: 10 · 2025: 5 · 2024: 6 · 2023: 15 · 2022: 13 · 2021: 7 · 2020: 12 · 2019: 9 · 2018: 11 · 2017: 12 · 2016: 14 · 2015: 15 · 2014: 16 · 2013: 14 · 2012: 1
FWCI: 5.86
Type: journal article
Language: en
Open access: green
www.ncbi.nlm.nih.gov
Licence: www.springer.com/tdm (tdm)
Locations: Cellular and Molecular Neurobiology (publishedVersion)
PubMed Central (publishedVersion)
PubMed (publishedVersion)
Europe PMC (PubMed Central) (acceptedVersion)
Funders: National Institute of Mental Health (MH 092438, K99MH092438, MH 40008, R00MH092438, R01MH040008)
Topics: Life Sciences › Neuroscience › Behavioral Neuroscience › Stress Responses and Cortisol
Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuropeptides and Animal Physiology
Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neurotransmitter Receptor Influence on Behavior
Keywords: sex differences, stress response, corticotropin-releasing factor, locus coeruleus, norepinephrine, hypothalamic-pituitary-adrenal axis, CRF1 receptor, gonadal hormones, major depressive disorder, post-traumatic stress disorder, hyperarousal, stress-related psychiatric disorders
MeSH terms: Corticotropin-Releasing Hormone, Female, Humans, Locus Coeruleus, Male, Sex Characteristics, Stress, Psychological, Signal Transduction, Receptors, Corticotropin-Releasing Hormone

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