Non-classical estrogen receptors action on human dermal fibroblasts.
OBJECTIVE
To study the possible non-genomic effect of selective estrogen receptor modulators on human dermal fibroblasts (HDF).


METHODS
WS1 cells were used to test the effect of raloxifene. The mRNA expressions of estrogen receptor (ER) α and β and G protein-coupled ER 1(GRP30) were examined by reverse transcription polymerase chain reaction. Apoptosis was identified by TUNEL assay and FACS analysis. MAPK and PI3 K/Akt pathways were determined by immunoblotting analysis.


RESULTS
Neither ERα nor ERβ, but GPR30 was detected in WS1 cells. Raloxifene increased apoptosis, which was blocked by pertussis toxin, an inhibitor of G protein, or by LY294002. Phosphorylated p38 MAPK and Akt were also increased after raloxifene treatment.


CONCLUSIONS
SERMs could induce apoptosis of HDF through G protein and PI3 K/Akt signaling, which may help understand the role of SERMs on the skin.
Department of Obstetrics and Gynecology, Kaohsiung Veterans General Hospital, Kaohsiung, Taiwan.
Kuan-Hao
KH
Tsui
Peng-Hui
PH
Wang
Chia-Kai
CK
Chen
Yi-Jen
YJ
Chen
Shih-Hwa
SH
Chiou
Yen-Jen
YJ
Sung
Hsin-Yang
HY
Li
D017209:Apoptosis / Q000187:drug effects*; D002460:Cell Line; D020405:Dermis / Q000166:cytology / Q000187:drug effects*; D047628:Estrogen Receptor alpha / Q000378:metabolism; D047629:Estrogen Receptor beta / Q000378:metabolism; D005347:Fibroblasts / Q000187:drug effects* / Q000378:metabolism; D006801:Humans; D015151:Immunoblotting; D020287:In Situ Nick-End Labeling; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D020849:Raloxifene Hydrochloride / Q000494:pharmacology*; D011960:Receptors, Estrogen / Q000378:metabolism; D043562:Receptors, G-Protein-Coupled / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D020845:Selective Estrogen Receptor Modulators / Q000494:pharmacology*
D047628:Estrogen Receptor alpha; D047629:Estrogen Receptor beta; D020928:Mitogen-Activated Protein Kinases; D019869:Phosphatidylinositol 3-Kinases; D051057:Proto-Oncogene Proteins c-akt; D020849:Raloxifene Hydrochloride; D011960:Receptors, Estrogen; D043562:Receptors, G-Protein-Coupled; D020845:Selective Estrogen Receptor Modulators; C506487:ESR1 protein, human; C109584:GPER1 protein, human