Cited by 69Estrogen and related hormone effectsProtein Kinase Regulation and GTPase SignalingSex and Gender in Healthcare

Sex-related differences in MAPKs activation in rat astrocytes: effects of estrogen on cell death

Zhang, Lei, Li, Beng shing, Zhao, Weqing, Chang, Yoong H, Ma, Wu, Dragan, M, Barker, Jeffery L, Hu, Qian +1 more·2002·Molecular Brain Research

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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Crossref · 10.1016/s0169-328x(02)00130-4

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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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