17β-Estradiol inhibits testosterone-induced cell proliferation in HepG2 by modulating the relative ratios of 3 estrogen receptor isoforms to the androgen receptor

2018 ◽  
Vol 119 (10) ◽  
pp. 8659-8671 ◽  
Author(s):  
Zhixiang Xu ◽  
Jun Liu ◽  
Cao Jianxin ◽  
Zhuang Yongliang ◽  
Xuejun Pan
Keyword(s):  
Cell Proliferation ◽  
Estrogen Receptor ◽  
Androgen Receptor ◽  
Receptor Isoforms ◽  
17Β Estradiol ◽  
Estrogen Receptor Isoforms

Expression of estrogen receptor isoforms in liver dendritic cells

2007 ◽  
Vol 39 (3) ◽  
pp. A16-A17
Author(s):  
A. Castellaneta ◽  
N. De Tullio ◽  
F. Gagliardi ◽  
M. Margiotta ◽  
S. Tanzi ◽  
...  
Keyword(s):  
Dendritic Cells ◽  
Estrogen Receptor ◽  
Receptor Isoforms ◽  
Estrogen Receptor Isoforms

scholarly journals 11-Ketotestosterone Is a Major Androgen Produced in Human Gonads

2016 ◽  
Vol 101 (10) ◽  
pp. 3582-3591 ◽  
Author(s):  
Yoshitaka Imamichi ◽  
Koh-ichi Yuhki ◽  
Makoto Orisaka ◽  
Takeshi Kitano ◽  
Kuniaki Mukai ◽  
...  
Keyword(s):  
Cell Proliferation ◽  
Estrogen Receptor ◽  
Cytochrome P450 ◽  
Androgen Receptor ◽  
Leydig Cells ◽  
Plasma Concentrations ◽  
Hydroxysteroid Dehydrogenase ◽  
Reproductive Age ◽  
Luciferase Reporter ◽  
Mcf 7

Context: 11-ketotestosterone (11-KT) is a novel class of active androgen. However, the detail of its synthesis remains unknown for humans. Objective: The objective of this study was to clarify the production and properties of 11-KT in human. Design, Participants, and Methods: Expression of cytochrome P450 and 11β-hydroxysteroid dehydrogenase types 1 and 2 (key enzymes involved in the synthesis of 11-KT) were investigated in human gonads. The production of 11-KT was investigated in Leydig cells. Plasma concentrations of testosterone and 11-KT were measured in 10 women and 10 men of reproductive age. Investigation of its properties was performed using breast cancer-derived MCF-7 cells. Results: Cytochrome P450 and 11β-hydroxysteroid dehydrogenase types 1 and 2 were detected in Leydig cells and theca cells. Leydig cells produced 11-KT, and relatively high levels of plasma 11-KT were measured in both men and women. There was no sexual dimorphism in the plasma levels of 11-KT, even though testosterone levels were more than 20 times higher in men than in women. It is noteworthy that the levels of testosterone and 11-KT were similar in women. In a luciferase reporter system, 11-KT activated human androgen receptor-mediated transactivation. Conversely, 11-KT did not activate estrogen receptor-mediated transactivation in aromatase-expressed MCF-7 cells, whereas testosterone did following conversion to estrogen. 11-KT did not affect the estrogen/estrogen receptor -mediated cell proliferation of MCF-7 cells. Furthermore, it significantly inhibited cell proliferation when androgen receptor was transfected into MCF-7 cells. Conclusions: The current study indicates that 11-KT is produced in the gonads and represents a major androgen in human. It can potentially serve as a nonaromatizable androgen.

scholarly journals Palmitoylation-dependent Estrogen Receptor α Membrane Localization: Regulation by 17β-Estradiol

2005 ◽  
Vol 16 (1) ◽  
pp. 231-237 ◽  
Author(s):  
Filippo Acconcia ◽  
Paolo Ascenzi ◽  
Alessio Bocedi ◽  
Enzo Spisni ◽  
Vittorio Tomasi ◽  
...  
Keyword(s):  
Cell Proliferation ◽  
Estrogen Receptor ◽  
Plasma Membrane ◽  
Estrogen Receptor Α ◽  
Membrane Localization ◽  
Target Cells ◽  
Dependent Manner ◽  
Caveolin 1 ◽  
17Β Estradiol

A fraction of the nuclear estrogen receptor α (ERα) is localized to the plasma membrane region of 17β-estradiol (E2) target cells. We previously reported that ERα is a palmitoylated protein. To gain insight into the molecular mechanism of ERα residence at the plasma membrane, we tested both the role of palmitoylation and the impact of E2 stimulation on ERα membrane localization. The cancer cell lines expressing transfected or endogenous human ERα (HeLa and HepG2, respectively) or the ERα nonpalmitoylable Cys447Ala mutant transfected in HeLa cells were used as experimental models. We found that palmitoylation of ERα enacts ERα association with the plasma membrane, interaction with the membrane protein caveolin-1, and nongenomic activities, including activation of signaling pathways and cell proliferation (i.e., ERK and AKT activation, cyclin D1 promoter activity, DNA synthesis). Moreover, E2 reduces both ERα palmitoylation and its interaction with caveolin-1, in a time- and dose-dependent manner. These data point to the physiological role of ERα palmitoylation in the receptor localization to the cell membrane and in the regulation of the E2-induced cell proliferation.

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