Novel Actions of Estrogen Receptor-β on Anxiety-Related Behaviors
Abstract
Estrogens are reported to have both anxiogenic and anxiolytic properties. This dichotomous neurobiological response to estrogens may be mediated by the existence of two distinct estrogen receptor (ER) systems, ERalpha and ERbeta. In brain, ERalpha plays a critical role in regulating reproductive neuroendocrine function, whereas ERbeta may be more important in regulating nonreproductive functions. To determine whether estrogen's anxiolytic actions could be mediated by ERbeta, we examined anxiety-related behaviors after treatment with ER subtype-selective agonists. Ovariectomized female rats, divided into four treatment groups, were injected with the selective ERbeta agonist diarylpropionitrile (DPN), the ERalpha-selective agonist propyl-pyrazole-triol (PPT), 17beta-estradiol, or vehicle daily for 4d. After injections, behavior was monitored in the elevated plus maze or open field. Rats treated with DPN showed significantly decreased anxiety-related behaviors in both behavioral paradigms. In the elevated plus maze, DPN significantly increased the number of open arm entries and time spent on the open arms of the maze. Furthermore, DPN significantly reduced, whereas PPT increased, anxiogenic behaviors such as the number of fecal boli and time spent grooming. In the open field, DPN-treated females made more rears, interacted more with a novel object, and spent more time in the middle of the open field than did control or PPT-treated rats. To confirm that DPN's anxiolytic actions a…
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ERβ in the PVN and associated structures, including the BnST, plays a fundamental role in mediating motivational and anxiety-related behaviors.
“Although the functional role of limbic ERβ remains ambiguous, ERβ in the PVN and associated structures, including the BnST, plays a fundamental role in mediating motivational and anxiety-related behaviors (134–136).”
From Endocrine Disruption of Vasopressin Systems and Related Behaviors (2017) · cites this paper as [134]
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“Again, it is likely that ERb receptors mediate the effects of estrogen on anxiety state as the ERb preferring SERM, DPN decreases anxiety-like behaviour in elevated plus maze and the open field whereas the ERa preferring PPT had an anxiogenic-like profile ( Lund et al., 2005 ).”
BackgroundSex and gender in psychoneuroimmunology research: Past, present and future
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“For example, estrogen has also been shown to modulate both anxiety (Bodo and Rissman, 2006; Lund et al., 2005) and depression (via neurotransmitters 5HT [serotonin] and dopamine) (Zhou et al., 2002) whereas testosterone has been more frequently linked with sexual behavior and behavioral aggression…”
BackgroundNumakawa, T., Richards, M., Nakajima, S., Adachi, N., Furuta, M., Odaka, H., & Kunugi, H. (2014) · Frontiers in Psychiatry · doi:10.3389/fpsyt.2014.00136 · Cited by 86 · see citing works
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“ER activation increases fear and anxiety behaviors, and ER activation reduces these behaviors (Morgan and Pfaff, 2001; Walf et al., 2004; Lund et al., 2005; Walf and Frye, 2005).”
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“…from the pituitary and corticosterone from the adrenal cortex) following exposure to a stressful situation (Handa et al., 1994; Lund et al., 2004; Lund et al., 2005; Lund et al., 2006), suggesting androgens can influence HPA axis activity, and in turn, may potentially influence anxiety-related…”
BackgroundInfluentialMinireview. Estrogen Receptor beta in Health and Disease1
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“Several studies have shown that gonadal hormone levels can significantly affect behavior on the elevated plus maze and on novelty tasks (Frye and Walf 2004; Lund et al. 2005).”
BackgroundEffect of ER-β gene disruption on estrogenic regulation of anxiety in female mice
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“…anxiety: Studies in rodents discovered that a particular isoform of the estrogen receptor (ERβ) decreases anxiety in females (Imwalle et al. 2005; Lund et al. 2005) while increased levels of circulating testosterone decrease anxiety in both sexes (Celec et al. 2015) via androgen receptors…”
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“…estradiol’s effects occur via actions at two well-described isoforms of the estrogen receptor (ER), ERa or ERb, which are expressed in different regions of the brain, and may drive HPA axis function in opposing ways, are not clear (Miller et al. 2004; Suzuki and Handa 2004, 2005; Lund et al. 2005).”
BackgroundRegulation of estrogen receptor beta activity and implications in health and disease
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Estrogen Receptors and the Regulation of Neural Stress Responses
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Self-citation
- Authors
- Lund, T. D., Rovis, T., Chung, W. C. J., & Handa, R. J.
- Affiliations
- Colorado State University (US)
- Corresponding author
- Lund, Trent D.
- Venue
- Endocrinology
- Publisher
- The Endocrine Society
- Published
- 2005-02
- Volume
- 146
- Issue
- 2
- Pages
- 797-807
- ISSN
- 0013-7227 (ISSN-L)
- 1945-7170
- OpenAlex
- W2162934389
- Cited by
- 436
- References
- 0
- Citations by year
- 2026: 5 · 2025: 8 · 2024: 20 · 2023: 13 · 2022: 19 · 2021: 16 · 2020: 14 · 2019: 10 · 2018: 34 · 2017: 17 · 2016: 18 · 2015: 18 · 2014: 20 · 2013: 29 · 2012: 25
- FWCI
- 11.07
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Endocrinology (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institute of Neurological Disorders and Stroke (R01NS039951)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Estrogen and related hormone effects
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neurotransmitter Receptor Influence on Behavior
- Social Sciences › Psychology › Social Psychology › Neuroendocrine regulation and behavior
- Keywords
- estrogen receptor beta, anxiety-like behavior, diarylpropionitrile, propyl pyrazole triol, estradiol, tamoxifen, elevated plus maze, open field, ovariectomized rats, estrogen receptor alpha
- MeSH terms
- Animals, Anxiety, Behavior, Animal, Binding, Competitive, Blood-Brain Barrier, Brain, Fear, Female, Male, Nitriles, Phenols, Propionates, Pyrazoles, Receptors, Progesterone, Uterus, Up-Regulation, Rats, Sprague-Dawley, Estrogen Receptor alpha, Estrogen Receptor beta, Rats
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