Role of P450 aromatase in sex-specific astrocytic cell death

Mingyue Liu, Patricia D. Hurn, Charles E. Roselli, Nabil J. Alkayed

Research output: Contribution to journalArticle

99 Scopus citations

Abstract

Female animals are protected from ischemic brain damage relative to age-matched males, in part through protection provided by endogenous estradiol. In brain, estradiol is produced from testosterone by cytochrome P450 aromatase (cyp 19), a steroid synthetic enzyme present in astrocytes. We tested the hypothesis that astrocytes derived from neonatal female rat brain are less susceptible than male cells to oxygen-glucose deprivation (OGD), and that this endogenous protection is associated with enhanced aromatase activity. Primary cultured cortical astrocytes were prepared from male and female rat pups separately and grown to confluence in estrogen-free media. Cell death in response to OGD, alone or in combination with hydrogen peroxide, lipopolysaccharides, interleukin-1β, tissue necrosis factor-α, or nitric oxide (NO) donor diethylenetriamine/nitric oxide adduct (DETA/NO) was quantified as the ratio of propidium iodide to calcein AM-positive cells. Aromatase activity and cyp19 mRNA and protein levels were measured in cultures from each sex. Female astrocytes are more resistant to OGD and oxidant cell death induced by H2O2 , but sustain greater cell death when inflammatory mediators are combined with OGD compared with OGD alone. Media transfer from female to male cells conferred protection against OGD-induced cell death. Aromatase activity and expression is greater in female than in male astrocytes. The aromatase inhibitor, Arimidex (100 nmol/L), abolishes sex differences in OGD-induced cell death, whereas treatment with 17β-estradiol (10 nmol/L) protects cells of either sex. We conclude that astrocytes isolated from neonatal cortex exhibit marked sex differences in sensitivity to OGD, in part because of enhanced aromatization and estradiol formation in female cells.

Original languageEnglish (US)
Pages (from-to)135-141
Number of pages7
JournalJournal of Cerebral Blood Flow and Metabolism
Volume27
Issue number1
DOIs
StatePublished - Jan 5 2007

Keywords

  • Aromatase
  • Astrocyte
  • Cell death
  • Sex

ASJC Scopus subject areas

  • Neurology
  • Clinical Neurology
  • Cardiology and Cardiovascular Medicine

Fingerprint Dive into the research topics of 'Role of P450 aromatase in sex-specific astrocytic cell death'. Together they form a unique fingerprint.

  • Cite this