Sex-related differences in MAPKs activation in rat astrocytes: effects of estrogen on cell death
Abstract
Gender-related differences in the unstimulated and estrogen-induced activation of the mitogen-activated protein kinases (MAPKs) ERK1 and ERK2, cell proliferation, and cell death were examined using rat cortical astrocytes in culture. Females have higher unstimulated levels of phosphorylated ERK1 and ERK2 than males. 17beta-Estradiol (E(2)) decreases activation of ERK1 and ERK2, with females showing a greater response than males. Further, E(2) results in more inhibition of DNA synthesis and greater increase in cell death in females than in males. The inhibitory effects of E(2) on DNA synthesis are mimicked and enhanced by a specific MAPK kinase (MEK) inhibitor, PD98059. Finally, the inhibitory effects of E(2) are blocked by the estrogen receptor antagonist tamoxifen in astrocytes from females but not males, with ER-alpha (estrogen receptor alpha) present in the former but not the latter. Taken together, these results suggest that the sex differences in unstimulated and estrogen-modulated activation of MAPKs may result in differential regulation of cell proliferation and death in astrocytes and possibly contribute to sexual dimorphisms in brain development.
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Self-citationGonadal Hormones and Behavior in Women: Concentrations versus Context
Rubinow, D. R., Schmidt, P. J., Meltzer-Brody, S. E., & Harsh, V. (2009) · Elsevier eBooks · doi:10.1016/b978-008088783-8.00076-0 · Cited by 4 · see citing works
Self-citationBielohuby, M., Sawitzky, M., Johnsen, I. K., Wittenburg, D., Beuschlein, F., Wolf, E., & Hoeflich, A. (2008) · Growth Hormone & IGF Research · doi:10.1016/s1096-6374(08)70149-7 · Cited by 2 · see citing works
Reproducible Sex Differences in Personalized Functional Network Topography in Youth
Keller, A. S., Sun, K. Y., Francisco, A., Robinson, H., Beydler, E., Bassett, D. S., Cieslak, M., Cui, Z., Davatzikos, C. A., Yong Fan, A., et al. (2025) · Biological Psychiatry · doi:10.1016/j.biopsych.2025.02.104 · Cited by 1 · see citing works
Steroid Metabolism in Glial Cells
Melcangi, R. C., & García‐Segura, L. M. (2008) · Springer eBooks · doi:10.1007/978-1-4020-6854-6_2 · Cited by 1 · see citing works
Neonatal Exposure to the Phytoestrogen Genistein Alters Ovarian Differentiation and Development
Jefferson, W. N. (2006) · NCSU Libraries Repository (North Carolina State University Libraries)
Chapter 2 Steroid Metabolism in Glial Cells
Melcangi, R. C., & García‐Segura, L. M. (2008)
- Authors
- Zhang, L., Li, B. S., Zhao, W., Chang, Y. H., Ma, W., Dragan, M., Barker, J. L., Hu, Q., & Rubinow, D. R.
- Affiliations
- National Institutes of Health (US)
- United States Naval Research Laboratory (US)
- Corresponding author
- Rubinow, David R
- Venue
- Molecular Brain Research
- Publisher
- Elsevier BV
- Published
- 2002-06
- Volume
- 103
- Issue
- 1-2
- Pages
- 1-11
- ISSN
- 0169-328X (ISSN-L)
- OpenAlex
- W2047934167
- Cited by
- 69
- References
- 48
- Citations by year
- 2025: 3 · 2022: 1 · 2021: 4 · 2020: 1 · 2019: 1 · 2018: 4 · 2017: 2 · 2016: 4 · 2015: 1 · 2014: 4 · 2013: 2 · 2012: 5
- FWCI
- 2.13
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Molecular Brain Research (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Estrogen and related hormone effects
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Protein Kinase Regulation and GTPase Signaling
- Health Sciences › Medicine › Public Health, Environmental and Occupational Health › Sex and Gender in Healthcare
- Keywords
- sex differences, astrocytes, mitogen-activated protein kinase, ERK1/ERK2, estradiol, estrogen receptor alpha, tamoxifen, MAPK kinase inhibition, PD98059, cell death, cell proliferation, DNA synthesis, sexual dimorphism, cortical astrocytes, brain development
- MeSH terms
- Animals, Astrocytes, Brain, Cell Division, Cells, Cultured, Estradiol, Sex Characteristics, Cell Death, Rats, Sprague-Dawley, Mitogen-Activated Protein Kinase 1, Mitogen-Activated Protein Kinases, Mitogen-Activated Protein Kinase 3, Rats
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