Major sex differences in non-genomic estrogen actions on intracellular signaling in mouse brain in vivo
Abstract
Rapid effects of estrogen have now been identified throughout the brain but the extent to which these actions may be different in males and females is unknown. Previous work has shown that estrogen rapidly phosphorylates Ser133 of cAMP responsive element binding protein (CREB) through a non-genomic mechanism. Using this indicator, we have examined here whether non-genomic estrogen actions occur in a sexually dimorphic manner within the adult brain. Male and female mice were gonadectomized and 3 weeks later treated with 17-beta-estradiol or vehicle for 1 h prior to perfusion fixation and subsequent CREB and phosphorylated CREB (pCREB) immunostaining of brain sections. The numbers of cells expressing CREB immunoreactivity were not altered by estrogen treatment or different in males and females in any of the brain regions examined. However, estrogen treatment significantly (P<0.05) increased pCREB-immunoreactive cell numbers in the medial preoptic area, ventrolateral division of the ventromedial nucleus, medial septum and CA1 region of the hippocampus of female mice. In contrast, estrogen increased pCREB levels in the medial septum and CA1 but not in the preoptic area or ventromedial nucleus of male mice. To evaluate the extent to which non-genomic estrogen actions may be sexually differentiated within a single neuronal phenotype, dual labeling immunocytochemistry was undertaken to evaluate the gonadotropin-releasing hormone (GnRH) neuronal phenotype. Estrogen significantly (P<0.05) increased the numbers of GnRH neurons expressing pCREB in female but not male mice. Together, these results demonstrate the existence of a marked sex difference in estrogen's non-genomic effects upon brain function in vivo.
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- Authors
- Ábrahám, I. M., & Herbison, A. E.
- Affiliations
- Eötvös Loránd University (HU)
- Babraham Institute (GB)
- Corresponding author
- Herbison, A.E.
- Venue
- Neuroscience
- Publisher
- Elsevier BV
- Published
- 2005-01
- Volume
- 131
- Issue
- 4
- Pages
- 945-951
- ISSN
- 0306-4522 (ISSN-L)
- OpenAlex
- W2025716332
- Cited by
- 73
- References
- 57
- Citations by year
- 2026: 1 · 2025: 1 · 2023: 2 · 2022: 2 · 2021: 1 · 2020: 1 · 2019: 3 · 2018: 3 · 2017: 2 · 2016: 4 · 2015: 4 · 2014: 1 · 2013: 2 · 2012: 4
- FWCI
- 3.94
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Neuroscience (publishedVersion)
- PubMed (publishedVersion)
- Nova Science Publishers (Nova Science Publishers, Inc.) (submittedVersion)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Estrogen and related hormone effects
- Health Sciences › Medicine › Reproductive Medicine › Hypothalamic control of reproductive hormones
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Sexual Differentiation and Disorders
- Keywords
- non-genomic estrogen signaling, sex differences, CREB phosphorylation, estradiol, GnRH neurons, medial preoptic area, ventromedial hypothalamus, medial septum, hippocampal CA1, gonadectomy, rapid estrogen signaling, mouse brain
- MeSH terms
- Animals, Brain, Brain Chemistry, Estradiol, Female, Immunohistochemistry, Gonadotropin-Releasing Hormone, Male, Mice, Inbred CBA, Mice, Inbred C57BL, Neurons, Orchiectomy, Ovariectomy, Phenotype, Phosphorylation, Sex Characteristics, Signal Transduction, Cyclic AMP Response Element-Binding Protein, Mice
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