PMID- 34399087
OWN - NLM
STAT- MEDLINE
DCOM- 20220209
LR  - 20220209
IS  - 1448-5990 (Electronic)
IS  - 1031-3613 (Linking)
VI  - 33
IP  - 12
DP  - 2021 Oct
TI  - Dexamethasone may inhibit placental growth by blocking glucocorticoid receptors 
      via phosphatidylinositol 3-kinase/AKT/mammalian target of rapamycin and reactive 
      oxygen species/AMP-activated protein kinase signalling pathways in human 
      placental JEG-3 cells.
PG  - 700-712
LID - 10.1071/RD21048 [doi]
AB  - This study explored the molecular mechanism underlying the effects of 
      dexamethasone (DEX, 1 microM) on glucose transporters (GLUT) in JEG-3 human placental 
      choriocarcinoma cells. JEG-3 cells were treated with DEX, an expression plasmid 
      encoding human glucocorticoid receptor alpha (GRalpha), pcDNA3.1-GRalpha, GRalpha short 
      interference (si) RNA, LY294002, xanthine oxidase (XO)/hypoxanthine (HX), 
      rapamycin, insulin-like growth factor (IGF) 1, N-acetylcysteine (NAC) or 
      phosphatidic acid (PA), and cell proliferation, apoptosis, mitochondrial membrane 
      potential (MMP), human chorionic gonadotrophin (hCG) content, human placental 
      lactogen (hPL) content, glucose uptake, reactive oxygen species levels and 
      signalling pathway modulation were evaluated. Treatment of JEG-3 cells with DEX 
      (1 microM), GRalpha siRNA, LY294002 (50 microM), XO/HX (7.2 microM/36 nM) or rapamycin (80 nM) 
      inhibited cell proliferation, induced apoptosis, significantly decreased MMP and 
      hCG and hPL content and increased ROS levels. In addition, glucose uptake was 
      decreased through downregulation of the mRNA and protein expression of GRalpha, GLUT1 
      and GLUT3. Treatment of JEG-3 cells with GRalpha siRNA, LY294002, XO/HX or rapamycin 
      inhibited phosphorylation of phosphatidylinositol 3-kinase (PI3K), Akt, glycogen 
      synthase kinase 3 and mammalian target of rapamycin (mTOR) and induced the 
      phosphorylation of AMP-activated protein kinase (AMPK) and tuberous sclerosis 
      complex 2. The effects of GRalpha overexpression and IGF1 (100 nM), NAC (5 nM) or PA 
      (100 microM) treatment on JEG-3 cells contrasted with those of DEX treatment. DEX 
      blocked glucose uptake by downregulating GRalpha expression, which reduced GLUT1 and 
      GLUT3 mRNA and protein expression, which, in turn, may have inhibited the 
      PI3K/AKT/mTOR pathway and activated the ROS/AMPK pathway.
FAU - Zhan, Xin
AU  - Zhan X
AD  - Department of Obstetrics and Gynecology, Affiliated Hangzhou First People's 
      Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang, China.
FAU - Xie, Yiran
AU  - Xie Y
AD  - Reproductive Medicine Center, Taihe Hospital, Hubei Medical University, Shiyan 
      442000, China.
FAU - Sun, Liping
AU  - Sun L
AD  - Department of Obstetrics and Gynecology, Affiliated Hangzhou First People's 
      Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang, China.
FAU - Si, Qi
AU  - Si Q
AD  - Department of Obstetrics and Gynecology, Affiliated Hangzhou First People's 
      Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang, China.
FAU - Shang, Hongkai
AU  - Shang H
AD  - Department of Obstetrics and Gynecology, Affiliated Hangzhou First People's 
      Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang, China; and 
      Corresponding author. Email: hongkaishang@zju.edu.cn.
LA  - eng
PT  - Journal Article
PL  - Australia
TA  - Reprod Fertil Dev
JT  - Reproduction, fertility, and development
JID - 8907465
RN  - 0 (Reactive Oxygen Species)
RN  - 0 (Receptors, Glucocorticoid)
RN  - 7S5I7G3JQL (Dexamethasone)
RN  - EC 2.7.11.1 (Proto-Oncogene Proteins c-akt)
RN  - EC 2.7.11.1 (TOR Serine-Threonine Kinases)
RN  - EC 2.7.11.31 (AMP-Activated Protein Kinases)
SB  - IM
MH  - AMP-Activated Protein Kinases/metabolism
MH  - Apoptosis/drug effects
MH  - Cell Line
MH  - Dexamethasone/*pharmacology
MH  - Female
MH  - Humans
MH  - Membrane Potential, Mitochondrial/drug effects
MH  - Phosphatidylinositol 3-Kinases/metabolism
MH  - Phosphorylation/drug effects
MH  - Placenta/*drug effects/metabolism
MH  - Pregnancy
MH  - Proto-Oncogene Proteins c-akt/metabolism
MH  - Reactive Oxygen Species/*metabolism
MH  - Receptors, Glucocorticoid/*metabolism
MH  - Signal Transduction/*drug effects
MH  - TOR Serine-Threonine Kinases/metabolism
EDAT- 2021/08/17 06:00
MHDA- 2022/02/10 06:00
CRDT- 2021/08/16 20:08
PHST- 2021/02/22 00:00 [received]
PHST- 2021/06/15 00:00 [accepted]
PHST- 2021/08/17 06:00 [pubmed]
PHST- 2022/02/10 06:00 [medline]
PHST- 2021/08/16 20:08 [entrez]
AID - RD21048 [pii]
AID - 10.1071/RD21048 [doi]
PST - ppublish
SO  - Reprod Fertil Dev. 2021 Oct;33(12):700-712. doi: 10.1071/RD21048.