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Journal article
Sex-Biased Stress Signaling: The Corticotropin-Releasing Factor Receptor as a Model
Molecular pharmacology, v 83(4), pp 737-745
01 Apr 2013
PMID: 23239826
Featured in Collection : UN Sustainable Development Goals @ Drexel
Abstract
Sex differences in the prevalence or severity of many diseases and in the response to pharmacological agents are well recognized. Elucidating the biologic bases of these differences can advance our understanding of the pathophysiology of disease and facilitate the development of treatments. Despite the importance to medicine, this has been an area of limited research. Here, we review physiologic, cellular, and molecular findings supporting the idea that there are sex differences in receptor signaling and trafficking that can be determinants of pathology. The focus is on the receptor for corticotropin-releasing factor (CRF), the orchestrator of the stress response, which has been implicated in diverse stress-related diseases that show a female prevalence. Data are reviewed that show sex differences in the association of the CRF receptor (CRF1) with the Gs protein and beta-arrestin 2 that would render females more responsive to acute stress and less able to adapt to chronic stress as a result of compromised CRF1 internalization. Because beta-arrestin 2 serves to link CRF1 to Gs-independent signaling pathways, this sex-biased signaling is proposed to result in distinct cellular responses to stress that are translated to different physiologic and behavioral coping mechanisms and that can have different pathologic consequences. Because stress has been implicated in diverse medical and psychiatric diseases, these sex differences in CRF1 signaling could explain sex differences in a multitude of disorders. The possibility that analogous sex differences may occur with other G-protein-coupled receptors underscores the impact of this effect and is discussed.
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Details
- Title
- Sex-Biased Stress Signaling: The Corticotropin-Releasing Factor Receptor as a Model
- Creators
- Rita J. Valentino - Children's Hospital of PhiladelphiaDebra Bangasser - Children's Hospital of PhiladelphiaElisabeth J. Van Bockstaele - Children's Hospital of Philadelphia
- Publication Details
- Molecular pharmacology, v 83(4), pp 737-745
- Publisher
- Amer Soc Pharmacology Experimental Therapeutics
- Number of pages
- 9
- Grant note
- R00MH092438 / NATIONAL INSTITUTE OF MENTAL HEALTH; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA; NIH National Institute of Mental Health (NIMH) MH040008; MH092438 / National Institutes of Health National Institute of Mental Health; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA; NIH National Institute of Mental Health (NIMH)
- Resource Type
- Journal article
- Language
- English
- Academic Unit
- Pharmacology and Physiology
- Web of Science ID
- WOS:000317574900004
- Scopus ID
- 2-s2.0-84875470081
- Other Identifier
- 991021903303004721
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- Collaboration types
- Domestic collaboration
- Web of Science research areas
- Pharmacology & Pharmacy