PMID- 21477953
OWN - NLM
STAT- MEDLINE
DCOM- 20111014
LR  - 20211203
IS  - 1873-2232 (Electronic)
IS  - 0378-4320 (Linking)
VI  - 125
IP  - 1-4
DP  - 2011 May
TI  - Activation of PI3K/mTOR signaling pathway contributes to induction of vascular 
      endothelial growth factor by hCG in bovine developing luteal cells.
PG  - 42-8
LID - 10.1016/j.anireprosci.2011.03.002 [doi]
AB  - We recently reported that HIF-1alpha plays a critical role in the regulation of 
      vascular endothelial growth factor (VEGF) expression in the developing letual 
      cells (LCs) and VEGF-dependent angiogenesis is essential for normal luteal 
      development. Although it is believed that hypoxia is the primary inducer of VEGF, 
      recent reports have also shown that human chorionic gonadotrophin (hCG) 
      up-regulates VEGF expression in developing corpus luteum (CL). Therefore the 
      present study was designed to test the induced effects of hCG on the expression 
      of VEGF and HIF-1alpha in LCs under normoxic and hypoxic conditions. In addition, we 
      also investigated whether the signaling pathways such as phosphatidylinositol 
      3-kinase (PI3K)/mammalian target of rapamycin (mTOR) and mitogen-activated 
      protein kinase (MAPK) are involved in hCG-induced VEGF in LCs. A significant 
      increase of VEGF mRNA was found in LCs treated with hCG, which was consistent 
      with the changes of HIF-1alpha protein, even under hypoxic conditions. However, there 
      was no obvious changes of HIF-1alpha mRNA in hCG-treated LCs between normoxic and 
      hypoxic conditions, indicating hCG induces VEGF expression by increasing 
      transcription of HIF-1alpha, while hypoxia mainly increases HIF-1alpha protein stability. 
      When LCs were pretreated with inhibitors, we found that the PI3K/mTOR signaling 
      pathway is required for HIF-1alpha and VEGF expression induced by hCG, while the MAPK 
      pathway is not required. Together, these results suggest that activation of 
      IP3K/mTOR signaling pathway contributes to the induction of VEGF and HIF-1alpha in 
      hCG-treated LCs. To our knowledge this will provide a new insight into the 
      important mechanism of hCG/LH-induced VEGF-dependent angiogenesis in the bovine 
      ovary.
CI  - Copyright (c) 2011 Elsevier B.V. All rights reserved.
FAU - Zhang, Zhenghong
AU  - Zhang Z
AD  - Department of Animal Science, College of Animal Science and Technology, Anhui 
      Science and Technology University, Bengbu 233100, China.
FAU - Yu, Debing
AU  - Yu D
FAU - Yin, Dingzhong
AU  - Yin D
FAU - Wang, Zhengchao
AU  - Wang Z
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20110315
PL  - Netherlands
TA  - Anim Reprod Sci
JT  - Animal reproduction science
JID - 7807205
RN  - 0 (Chorionic Gonadotropin)
RN  - 0 (Hypoxia-Inducible Factor 1, alpha Subunit)
RN  - 0 (Phosphoinositide-3 Kinase Inhibitors)
RN  - 0 (Protein Kinase Inhibitors)
RN  - 0 (Vascular Endothelial Growth Factor A)
RN  - 63231-63-0 (RNA)
RN  - EC 2.7.11.1 (TOR Serine-Threonine Kinases)
SB  - IM
MH  - Animals
MH  - Blotting, Western/veterinary
MH  - Cattle/*physiology
MH  - Chorionic Gonadotropin/*pharmacology
MH  - Corpus Luteum/cytology/drug effects/enzymology/*metabolism
MH  - Enzyme Activation/drug effects
MH  - Female
MH  - Hypoxia-Inducible Factor 1, alpha Subunit/biosynthesis/genetics
MH  - Luteal Cells/drug effects/enzymology/*metabolism
MH  - Phosphatidylinositol 3-Kinases/*metabolism
MH  - Phosphoinositide-3 Kinase Inhibitors
MH  - Protein Kinase Inhibitors/pharmacology
MH  - RNA/chemistry/genetics
MH  - Reverse Transcriptase Polymerase Chain Reaction/veterinary
MH  - Signal Transduction/drug effects
MH  - TOR Serine-Threonine Kinases/*metabolism
MH  - Vascular Endothelial Growth Factor A/*biosynthesis/genetics
EDAT- 2011/04/12 06:00
MHDA- 2011/10/15 06:00
CRDT- 2011/04/12 06:00
PHST- 2010/08/09 00:00 [received]
PHST- 2011/02/28 00:00 [revised]
PHST- 2011/03/07 00:00 [accepted]
PHST- 2011/04/12 06:00 [entrez]
PHST- 2011/04/12 06:00 [pubmed]
PHST- 2011/10/15 06:00 [medline]
AID - S0378-4320(11)00072-8 [pii]
AID - 10.1016/j.anireprosci.2011.03.002 [doi]
PST - ppublish
SO  - Anim Reprod Sci. 2011 May;125(1-4):42-8. doi: 10.1016/j.anireprosci.2011.03.002. 
      Epub 2011 Mar 15.