PMID- 25739982
OWN - NLM
STAT- MEDLINE
DCOM- 20160111
LR  - 20220317
IS  - 1098-2795 (Electronic)
IS  - 1040-452X (Linking)
VI  - 82
IP  - 4
DP  - 2015 Apr
TI  - mTOR is involved in 17beta-estradiol-induced, cultured immature boar Sertoli cell 
      proliferation via regulating the expression of SKP2, CCND1, and CCNE1.
PG  - 305-14
LID - 10.1002/mrd.22473 [doi]
AB  - Mammalian target of rapamycin (mTOR) is known to be involved in mammalian cell 
      proliferation, while S-phase kinase-associated protein 2 (SKP2) plays a vital 
      role in the cell cycle. Within the testis, estrogen also plays an important role 
      in Sertoli cell proliferation, although it is not clear how. The present study 
      asked if mTOR is involved in 17beta-estradiol-dependent Sertoli cell proliferation. 
      We specifically assessed if extracellular signal-regulated kinase 1/2 (ERK1/2) 
      and/or phosphoinositide 3-kinase/protein kinase B (PI3K/AKT) exert convergent 
      effects toward the activation of mTOR signaling, and if this signaling regulates 
      the expression of SKP2 through retinoblastoma (RB) and early mitotic inhibitor 1 
      (EMI1) protein and on CCNE1 and CCND1 mRNA levels. Treatment with 17beta-estradiol 
      for 15-90 min activated mTOR, with mTOR phosphorylation peaking after 30 min. 
      U0126 (5 muM), a specific inhibitor of (MEK1/2), and 10-DEBC (2 muM), a selective 
      inhibitor of AKT, both significantly reduced 17beta-estradiol-induced 
      phosphorylation of mTOR. Rapamycin suppressed 17beta-estradiol-induced Sertoli cell 
      proliferation, appearing to act by reducing the abundance of SKP2, CCND1, and 
      CCNE1 mRNA as well as RB and EMI1 protein. These data indicated that 
      17beta-estradiol enhances Sertoli cell proliferation via mTOR activation, which 
      involves both ERK1/2 and PI3K/AKT signaling. Activated mTOR subsequently 
      increases SKP2 mRNA and protein expression by enhancing the expression of CCND1 
      and CCNE1, and inhibits SKP2 protein degradation by increasing EMI1 abundance.
CI  - (c) 2015 Wiley Periodicals, Inc.
FAU - Yang, Wei-Rong
AU  - Yang WR
AD  - College of Animal Science and Technology, Southwest University, Chongqing, P. R. 
      China; Chongqing Key Laboratory of Forage and Herbivore, Southwest University, 
      Chongqing, P. R. China.
FAU - Wang, Yong
AU  - Wang Y
FAU - Wang, Yi
AU  - Wang Y
FAU - Zhang, Jiao-Jiao
AU  - Zhang JJ
FAU - Zhang, Jia-Hua
AU  - Zhang JH
FAU - Lu, Cheng
AU  - Lu C
FAU - Wang, Xian-Zhong
AU  - Wang XZ
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20150304
PL  - United States
TA  - Mol Reprod Dev
JT  - Molecular reproduction and development
JID - 8903333
RN  - 0 (Cyclin E)
RN  - 0 (DNA Primers)
RN  - 0 (S-Phase Kinase-Associated Proteins)
RN  - 136601-57-5 (Cyclin D1)
RN  - 4TI98Z838E (Estradiol)
RN  - EC 2.7.11.1 (TOR Serine-Threonine Kinases)
SB  - IM
MH  - Analysis of Variance
MH  - Animals
MH  - Blotting, Western
MH  - Cell Proliferation/*physiology
MH  - Cyclin D1/metabolism
MH  - Cyclin E/metabolism
MH  - DNA Primers/genetics
MH  - Estradiol/*metabolism/pharmacology
MH  - Gene Expression Regulation/drug effects/*physiology
MH  - Male
MH  - Phosphorylation/drug effects
MH  - Real-Time Polymerase Chain Reaction
MH  - Reverse Transcriptase Polymerase Chain Reaction
MH  - S-Phase Kinase-Associated Proteins/metabolism
MH  - Sertoli Cells/metabolism/*physiology
MH  - Sus scrofa/*physiology
MH  - TOR Serine-Threonine Kinases/*metabolism
EDAT- 2015/03/06 06:00
MHDA- 2016/01/12 06:00
CRDT- 2015/03/06 06:00
PHST- 2014/12/01 00:00 [received]
PHST- 2015/02/12 00:00 [accepted]
PHST- 2015/03/06 06:00 [entrez]
PHST- 2015/03/06 06:00 [pubmed]
PHST- 2016/01/12 06:00 [medline]
AID - 10.1002/mrd.22473 [doi]
PST - ppublish
SO  - Mol Reprod Dev. 2015 Apr;82(4):305-14. doi: 10.1002/mrd.22473. Epub 2015 Mar 4.