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

Lei Zhang; Beng shing Li; Weqing Zhao; Yoong H. Chang; Wu Ma; M. Dragan; Jeffery L. Barker; Qian Hu; David R. Rubinow

doi:10.1016/S0169-328X(02)00130-4

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

Lei Zhang, Beng shing Li, Weqing Zhao, Yoong H. Chang, Wu Ma, M. Dragan, Jeffery L. Barker, Qian Hu, David R. Rubinow

Psychiatry

Research output: Contribution to journal › Article › peer-review

64 Scopus citations

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. 17β-Estradiol (E₂) decreases activation of ERK1 and ERK2, with females showing a greater response than males. Further, E₂ results in more inhibition of DNA synthesis and greater increase in cell death in females than in males. The inhibitory effects of E₂ on DNA synthesis are mimicked and enhanced by a specific MAPK kinase (MEK) inhibitor, PD98059. Finally, the inhibitory effects of E₂ are blocked by the estrogen receptor antagonist tamoxifen in astrocytes from females but not males, with ER-α (estrogen receptor α) 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.

Original language	English
Pages (from-to)	1-11
Number of pages	11
Journal	Molecular Brain Research
Volume	103
Issue number	1-2
DOIs	https://doi.org/10.1016/S0169-328X(02)00130-4
State	Published - 30 Jun 2002

Keywords

Astrocyte
Cell death
Estrogen
Kinases
Proliferation
Sexual dimorphism

Access to Document

10.1016/S0169-328X(02)00130-4

Cite this

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title = "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. 17β-Estradiol (E2) decreases activation of ERK1 and ERK2, with females showing a greater response than males. Further, E2 results in more inhibition of DNA synthesis and greater increase in cell death in females than in males. The inhibitory effects of E2 on DNA synthesis are mimicked and enhanced by a specific MAPK kinase (MEK) inhibitor, PD98059. Finally, the inhibitory effects of E2 are blocked by the estrogen receptor antagonist tamoxifen in astrocytes from females but not males, with ER-α (estrogen receptor α) 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.",

keywords = "Astrocyte, Cell death, Estrogen, Kinases, Proliferation, Sexual dimorphism",

author = "Lei Zhang and Li, {Beng shing} and Weqing Zhao and Chang, {Yoong H.} and Wu Ma and M. Dragan and Barker, {Jeffery L.} and Qian Hu and Rubinow, {David R.}",

year = "2002",

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T1 - Sex-related differences in MAPKs activation in rat astrocytes

T2 - Effects of estrogen on cell death

AU - Zhang, Lei

AU - Li, Beng shing

AU - Zhao, Weqing

AU - Chang, Yoong H.

AU - Ma, Wu

AU - Dragan, M.

AU - Barker, Jeffery L.

AU - Hu, Qian

AU - Rubinow, David R.

PY - 2002/6/30

Y1 - 2002/6/30

N2 - 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. 17β-Estradiol (E2) decreases activation of ERK1 and ERK2, with females showing a greater response than males. Further, E2 results in more inhibition of DNA synthesis and greater increase in cell death in females than in males. The inhibitory effects of E2 on DNA synthesis are mimicked and enhanced by a specific MAPK kinase (MEK) inhibitor, PD98059. Finally, the inhibitory effects of E2 are blocked by the estrogen receptor antagonist tamoxifen in astrocytes from females but not males, with ER-α (estrogen receptor α) 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.

AB - 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. 17β-Estradiol (E2) decreases activation of ERK1 and ERK2, with females showing a greater response than males. Further, E2 results in more inhibition of DNA synthesis and greater increase in cell death in females than in males. The inhibitory effects of E2 on DNA synthesis are mimicked and enhanced by a specific MAPK kinase (MEK) inhibitor, PD98059. Finally, the inhibitory effects of E2 are blocked by the estrogen receptor antagonist tamoxifen in astrocytes from females but not males, with ER-α (estrogen receptor α) 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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KW - Estrogen

KW - Kinases

KW - Proliferation

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