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Estrogens cause rapid activation of IP3-PKC-alpha signal transduction pathway in HEPG2 cells

M Marino1, V Pallottini, A Trentalance

  • 1Department of Biologia, Università "Roma 3,", v.le Marconi, 446, Rome, 00146, Italy.

Biochemical and Biophysical Research Communications
|May 16, 1998
PubMed

Insights

Estrogen rapidly increases inositol trisphosphate (IP3) production and protein kinase C-alpha (PKC-alpha) levels in liver cells. This rapid signaling pathway in human hepatoma cells requires a revised understanding of estrogen

Area of Science:

  • Endocrinology
  • Cell Biology
  • Molecular Pharmacology

Background:

  • The classic model of steroid hormone action involves slow genomic effects.
  • Emerging evidence suggests rapid, non-genomic actions of steroids, including estrogen.
  • The interplay between rapid and slow estrogen signaling pathways remains unclear.

Purpose of the Study:

  • To investigate the rapid effects of estrogen on inositol trisphosphate (IP3) production and PKC-alpha localization in HEPG2 cells.
  • To determine if these rapid effects are mediated by known estrogen signaling inhibitors.
  • To explore the downstream cellular consequences of rapid estrogen signaling.

Main Methods:

  • HEPG2 cells were treated with estrogen.
  • Inositol trisphosphate (IP3) production was measured.
  • Protein kinase C-alpha (PKC-alpha) levels on the membrane fraction were assessed.
  • Tyrosine-kinase inhibitor genisteine and anti-estrogen ICI 182,780 were used to block pathways.

Main Results:

  • Estrogen rapidly increased IP3 production in HEPG2 cells.
  • This effect was blocked by genisteine and ICI 182,780.
  • Increased membrane-bound PKC-alpha was observed 30 minutes after estrogen exposure.
  • These rapid signals can potentially modulate ion channels and cell proliferation.

Conclusions:

  • Estrogen triggers rapid IP3 production in human hepatoma cells, a novel finding.
  • This rapid signaling pathway involves tyrosine kinase and estrogen receptors.
  • The discovery necessitates a revision of the current models of estrogen action on target cells.

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