PMID- 17470519
OWN - NLM
STAT- MEDLINE
DCOM- 20070614
LR  - 20161124
IS  - 0022-0795 (Print)
IS  - 0022-0795 (Linking)
VI  - 193
IP  - 2
DP  - 2007 May
TI  - Corticotropin-releasing hormone or dexamethasone regulates rat 
      proopiomelanocortin transcription through Tpit/Pitx-responsive element in its 
      promoter.
PG  - 279-90
AB  - Tpit/Pitx-responsive element (Tpit/PitxRE), which binds transcription factors 
      Tpit and Pitx1, confers cell-type specific expression of proopiomelanocortin 
      (POMC) gene in pituitary corticotrops where the gene expression is mainly 
      regulated by corticotropin-releasing hormone (CRH) and glucocorticoids (Gcs). CRH 
      stimulates POMC gene expression, which is mediated by the accumulation of 
      intracellular cAMP and requires binding of Nur factors to Nur-responsive element 
      (NurRE). Gcs antagonize NurRE-dependent POMC gene expression through direct 
      interaction between glucocorticoid receptors and Nur factors. We examined whether 
      Tpit/PitxRE and NurRE are involved in CRH/cAMP-induced activation and Gc-induced 
      repression of POMC gene expression by reporter assay in AtT-20 corticotropic 
      cells. Deletion and mutation of Tpit/PitxRE markedly reduced basal activity of 
      the promoter, and those of NurRE decreased the levels of the CRH/cAMP-induced 
      activation. Nifedipine, KN-62, and W-7, specific inhibitors of the L-type calcium 
      channel, calmodulin-dependent protein kinase II, and calmodulin respectively, 
      attenuated CRH/cAMP-induced activation of promoters with three copies of either 
      Tpit/PitxRE or NurRE, indicating that both Tpit/PitxRE and NurRE mediate 
      CRH-induced activation of POMC gene expression in a calcium-dependent manner. 
      Deletion and mutation of Tpit/PitxRE abolished dexamethasone (DEX)-induced 
      repression of POMC gene expression, while those of NurRE did not, indicating that 
      Tpit/PitxRE predominantly mediates Gc-induced repression of POMC transcription. 
      However, DEX treatment attenuated activities of promoters with three copies of 
      either Tpit/PitxRE or NurRE, suggesting that Gcs act at NurRE as well as 
      Tpit/PitxRE to repress POMC gene expression. We conclude that Tpit/PitxRE is an 
      important element by which CRH and Gcs regulate the POMC gene expression.
FAU - Murakami, Itsuo
AU  - Murakami I
AD  - Department of Biology, Faculty of Science, Okayama University, 3-1-1, 
      Tsusima-naka, Okayama, Japan.
FAU - Takeuchi, Sakae
AU  - Takeuchi S
FAU - Kudo, Toshiyuki
AU  - Kudo T
FAU - Sutou, Shizuyo
AU  - Sutou S
FAU - Takahashi, Sumio
AU  - Takahashi S
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 (Calcium Channel Blockers)
RN  - 0 (Calmodulin)
RN  - 0 (Glucocorticoids)
RN  - 0 (Homeodomain Proteins)
RN  - 0 (Paired Box Transcription Factors)
RN  - 0 (RNA, Messenger)
RN  - 0 (Sulfonamides)
RN  - 0 (T-Box Domain Proteins)
RN  - 0 (TBX19 protein, human)
RN  - 0 (homeobox protein PITX1)
RN  - 63HM46XPOW (KN 62)
RN  - 65595-90-6 (W 7)
RN  - 66796-54-1 (Pro-Opiomelanocortin)
RN  - 7S5I7G3JQL (Dexamethasone)
RN  - 84477-87-2 (1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine)
RN  - 9015-71-8 (Corticotropin-Releasing Hormone)
RN  - E0399OZS9N (Cyclic AMP)
RN  - EC 2.7.11.17 (Calcium-Calmodulin-Dependent Protein Kinase Type 2)
RN  - EC 2.7.11.17 (Calcium-Calmodulin-Dependent Protein Kinases)
RN  - I9ZF7L6G2L (Nifedipine)
SB  - IM
MH  - 1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine/analogs & derivatives/pharmacology
MH  - Animals
MH  - Calcium Channel Blockers/pharmacology
MH  - Calcium-Calmodulin-Dependent Protein Kinase Type 2
MH  - Calcium-Calmodulin-Dependent Protein Kinases/antagonists & inhibitors
MH  - Calmodulin/antagonists & inhibitors
MH  - Cell Line
MH  - Corticotropin-Releasing Hormone/*pharmacology
MH  - Cyclic AMP/metabolism
MH  - Dexamethasone/*pharmacology
MH  - Gene Deletion
MH  - *Gene Expression Regulation
MH  - Glucocorticoids/*pharmacology
MH  - Homeodomain Proteins/genetics/*metabolism
MH  - Nifedipine/pharmacology
MH  - Paired Box Transcription Factors/genetics/metabolism
MH  - Pro-Opiomelanocortin/*genetics
MH  - Promoter Regions, Genetic
MH  - RNA, Messenger/analysis
MH  - Rats
MH  - Reverse Transcriptase Polymerase Chain Reaction
MH  - Sulfonamides/pharmacology
MH  - T-Box Domain Proteins/genetics/*metabolism
MH  - Transfection
EDAT- 2007/05/02 09:00
MHDA- 2007/06/15 09:00
CRDT- 2007/05/02 09:00
PHST- 2007/05/02 09:00 [pubmed]
PHST- 2007/06/15 09:00 [medline]
PHST- 2007/05/02 09:00 [entrez]
AID - 193/2/279 [pii]
AID - 10.1677/JOE-06-0143 [doi]
PST - ppublish
SO  - J Endocrinol. 2007 May;193(2):279-90. doi: 10.1677/JOE-06-0143.