Hepatic stellate cells contain the functional estrogen receptor beta but not the estrogen receptor alpha in male and female rats.
In an earlier study, we showed that estradiol (E2) inhibits proliferation and transformation in cultured rat hepatic stellate cells (HSCs) and that the actions of E2 are mediated through estrogen receptors (ERs). This study reports on an investigation of the cellular localization of ER subtypes ERalpha and ERbeta using immunohistochemistry in experimental fibrotic liver rats and of each ER subtype expression in cultured rat HSCs by evaluating the produced mRNA and protein. The results indicate that high levels of ERbeta expression and low or no levels of ERalpha expression were observed in normal and fibrotic livers and in quiescent and activated HSCs from both males and females. The specificity of E2-mediated antiapoptotic induction through the ERbeta was shown by dose-dependent inhibition by the pure ER antagonist ICI 182,780 in HSCs which were undergoing early apoptosis. These findings demonstrate for the first time that rat HSCs possess functional Erbeta, but not Eralpha, to respond directly to E2 exposure.
Zhou
Y
Y
Second Department of Internal Medicine, Tokushima University School of Medicine, Kuramoto-cho, Tokushima, 770-8503, Japan.
Shimizu
I
I
Lu
G
G
Itonaga
M
M
Okamura
Y
Y
Shono
M
M
Honda
H
H
Inoue
S
S
Muramatsu
M
M
Ito
S
S
D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D001667:Binding, Competitive; D015153:Blotting, Western; D002455:Cell Division; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D004958:Estradiol / Q000031:analogs & derivatives / Q000494:pharmacology; D047628:Estrogen Receptor alpha; D047629:Estrogen Receptor beta; D005260:Female; D005434:Flow Cytometry; D000077267:Fulvestrant; D022781:Hepatocytes / Q000737:chemistry* / Q000378:metabolism; D007150:Immunohistochemistry; D008099:Liver / Q000166:cytology* / Q000378:metabolism; D008297:Male; D008564:Membrane Potentials; D018613:Microscopy, Confocal; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D011960:Receptors, Estrogen / Q000037:antagonists & inhibitors / Q000096:biosynthesis* / Q000737:chemistry; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012737:Sex Factors
D047628:Estrogen Receptor alpha; D047629:Estrogen Receptor beta; D019253:Proto-Oncogene Proteins c-bcl-2; D012333:RNA, Messenger; D011960:Receptors, Estrogen; D000077267:Fulvestrant; D004958:Estradiol