Estrogens cause rapid activation of IP3-PKC-alpha signal transduction pathway in HEPG2 cells.
The mechanisms through which steroids affect target cells are not fully understood. In addition to the classic model, there is now increasing evidence that steroids can exert rapid actions. It must still be elucidated if rapid and slow estrogen actions produce co-operative and/or integrative functions. The effects of estrogen on inositol trisphosphate (IP3) production and PKC-alpha levels on membrane in the HEPG2 cell line have been investigated. Results show that estrogen addition to HEPG2 cells causes a rapid increase of IP3 production. The effect was totally inhibited by pre-incubation with tyrosine-kinase inhibitor genisteine and with the anti-estrogen ICI 182,780. An increased PKC-alpha level on the membrane fraction was present 30 min after estrogen exposure. The strong signal could elicit a variety of cellular responses such as modulation of ion channel, stimulation of cell proliferation, and phosphorylation of cytosolic ER. The ability of estrogen to trigger IP3 production in human hepatoma cells is a novel aspect of estrogen action that requires the current model of hormone stimulation target cells to be revised.
Marino
M
M
Department of Biologia, Università "Roma 3,", v.le Marconi, 446, Rome, 00146, Italy.
Pallottini
V
V
Trentalance
A
A
D006528:Carcinoma, Hepatocellular / Q000378:metabolism*; D004791:Enzyme Inhibitors / Q000494:pharmacology; D004958:Estradiol / Q000031:analogs & derivatives / Q000494:pharmacology; D004965:Estrogen Antagonists / Q000494:pharmacology; D004967:Estrogens / Q000494:pharmacology*; D000077267:Fulvestrant; D019833:Genistein / Q000494:pharmacology; D006801:Humans; D007294:Inositol / Q000378:metabolism; D015544:Inositol 1,4,5-Trisphosphate / Q000378:metabolism*; D007527:Isoenzymes / Q000037:antagonists & inhibitors / Q000378:metabolism*; D011374:Progesterone / Q000494:pharmacology; D011493:Protein Kinase C / Q000037:antagonists & inhibitors / Q000378:metabolism*; D051571:Protein Kinase C-alpha; D015398:Signal Transduction / Q000187:drug effects*; D014407:Tumor Cells, Cultured
D004791:Enzyme Inhibitors; D004965:Estrogen Antagonists; D004967:Estrogens; D007527:Isoenzymes; D000077267:Fulvestrant; D011374:Progesterone; D007294:Inositol; D004958:Estradiol; D015544:Inositol 1,4,5-Trisphosphate; D019833:Genistein; C496628:PRKCA protein, human; D011493:Protein Kinase C; D051571:Protein Kinase C-alpha