PMID- 11739023
OWN - NLM
STAT- MEDLINE
DCOM- 20020122
LR  - 20190709
IS  - 0022-0795 (Print)
IS  - 0022-0795 (Linking)
VI  - 171
IP  - 3
DP  - 2001 Dec
TI  - Stimulation of extracellular signal-regulated kinase by pituitary adenylate 
      cyclase-activating polypeptide in alpha T3-1 gonadotrophs.
PG  - R5-10
AB  - The putative hypophysiotropic factor pituitary adenylate cyclase-activating 
      polypeptide (PACAP) stimulates glycoprotein hormone alpha-subunit (alpha GSU) 
      gene transcription and secretion in the clonal gonadotroph alpha T3-1 cell line. 
      The specific signalling pathways regulating these actions of PACAP have not been 
      clearly defined. We have examined the possibility that mitogen activated protein 
      kinases (MAPKs) may play a role in mediating the effects of PACAP on alpha T3-1 
      gonadotrophs. Treatment of alpha T3-1 cells with PACAP (100 nM) or epidermal 
      growth factor (EGF, 10 nM) for 5 min significantly stimulated extracellular 
      signal-regulated kinase activity (ERK, a component of the MAPK pathway) as 
      determined by an immunocomplex assay. Pre-treatment of alpha T3-1 cells with the 
      specific MAPK kinase (MEK) inhibitor, U0126, blocked PACAP and EGF-induced 
      activation of ERK. Transcriptional stimulation of a human alpha GSU-luciferase 
      reporter construct by PACAP was unaffected by U0126 treatment. However, 
      pre-treatment with U0126 significantly inhibited PACAP stimulation of 
      [(3)H]-thymidine incorporation in alpha T3-1 cells. Thus our results suggest that 
      PACAP stimulates ERK activation in alpha T3-1 cells, and that the functional 
      effect of this ERK activation is increased DNA synthesis and cell proliferation 
      rather then transcriptional activation of the alpha GSU gene.
FAU - Fowkes, R C
AU  - Fowkes RC
AD  - Department of Endocrinology, St Bartholomew's & the Royal London School of 
      Medicine & Dentistry, Queen Mary, University of London, London EC1A 7BE, UK. 
      r.c.fowkes@mds.qmw.ac.uk
FAU - Burch, J
AU  - Burch J
FAU - Burrin, J M
AU  - Burrin JM
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - England
TA  - J Endocrinol
JT  - The Journal of endocrinology
JID - 0375363
RN  - 0 (Adcyap1 protein, mouse)
RN  - 0 (Butadienes)
RN  - 0 (Enzyme Inhibitors)
RN  - 0 (Neuropeptides)
RN  - 0 (Nitriles)
RN  - 0 (Pituitary Adenylate Cyclase-Activating Polypeptide)
RN  - 0 (U 0126)
RN  - EC 2.7.11.24 (Mitogen-Activated Protein Kinases)
SB  - IM
MH  - Animals
MH  - Butadienes/pharmacology
MH  - Cell Culture Techniques
MH  - Cell Line
MH  - Enzyme Inhibitors/pharmacology
MH  - Mice
MH  - Mitogen-Activated Protein Kinases/*metabolism
MH  - Neuropeptides/antagonists & inhibitors/*pharmacology
MH  - Nitriles/pharmacology
MH  - Pituitary Adenylate Cyclase-Activating Polypeptide
MH  - Pituitary Gland, Anterior/cytology/*drug effects/enzymology
EDAT- 2001/12/12 10:00
MHDA- 2002/01/23 10:01
CRDT- 2001/12/12 10:00
PHST- 2001/12/12 10:00 [pubmed]
PHST- 2002/01/23 10:01 [medline]
PHST- 2001/12/12 10:00 [entrez]
AID - JOE04581 [pii]
AID - 10.1677/joe.0.171r005 [doi]
PST - ppublish
SO  - J Endocrinol. 2001 Dec;171(3):R5-10. doi: 10.1677/joe.0.171r005.