Effects of sex hormones on regulation of ABCG2 expression in the placental cell line BeWo.
OBJECTIVE
The aim of this study was to elucidate the effects of sex hormones that are secreted during gestation from the placenta on ABCG2 mRNA and protein expression levels by using the placental cell line BeWo.


METHODS
We investigated the effects of estrogens (estrone, 17-beta-estradiol and estriol) on the expression level of ABCG2 mRNA by RT-PCR. The expression level of ABCG2 protein was analyzed by Western blot analysis. We also investigated the localization of ABCG2 in BeWo cells by Western blot analysis of the plasma membrane fraction and by immunohistochemistry.


RESULTS
It was found that all estrogens induce the expression of ABCG2 mRNA in a concentration-dependent manner. Furthermore, Western blot analysis showed that 17-beta-estradiol induces the expression of ABCG2 protein. Western blot analysis of the plasma membrane fraction and immunohistochemistry showed that ABCG2 localized on only the apical side of BeWo cells and that 17-beta-estradiol had no effect on the localization of ABCG2. In addition, progesterone suppressed the induction of ABCG2 expression by 17-beta-estradiol at 1-10 microM.


CONCLUSIONS
The expression of ABCG2 in the placenta is regulated by estrogen and progesterone during gestation.
Yasuda
Satoru
S
Department of Clinical Pharmaceutics and Therapeutics, Graduate School of Pharmaceutical Sciences, Hokkaido University, Sapporo, Japan.
Itagaki
Shirou
S
Hirano
Takeshi
T
Iseki
Ken
K
D000070997:ATP Binding Cassette Transporter, Subfamily G, Member 2; D018528:ATP-Binding Cassette Transporters / Q000235:genetics / Q000378:metabolism*; D002460:Cell Line; D045744:Cell Line, Tumor; D004967:Estrogens / Q000494:pharmacology; D015870:Gene Expression / Q000187:drug effects* / Q000502:physiology; D012739:Gonadal Steroid Hormones / Q000494:pharmacology*; D006801:Humans; D009363:Neoplasm Proteins / Q000235:genetics / Q000378:metabolism*; D010920:Placenta / Q000473:pathology*
C116614:ABCG2 protein, human; D000070997:ATP Binding Cassette Transporter, Subfamily G, Member 2; D018528:ATP-Binding Cassette Transporters; D004967:Estrogens; D012739:Gonadal Steroid Hormones; D009363:Neoplasm Proteins