Abstract
We attempted to elucidate molecular mechanisms of gonadotropin-releasing hormone (GnRH) gene regulation by the protein kinase C (PKC) pathway in GT1- 1 cells. Activation of PKC with 12-tetra-decanoylphorbol-13-acetate (TPA) or inhibition with staurosporine or calphostin C down-regulated GnRH mRNA levels. A serial deletion mutant analysis revealed that this suppression was mediated by the proximal region (-187/-69) of the mouse GnRH promoter. TPA transiently induced c-fos mRNA, whereas staurosporine or calphostin C failed to do so. However, PKC inhibitors blocked the TPA-evoked c-fos induction. Over-expression of PKCα down-regulated GnRH promoter activity, indicating that PKC activation was sufficient to inhibit GnRH gene expression. These results suggest that both activation and inhibition of PKC decrease the GnRH gene expression in the GT1-1 cells probably through different signal cascade mechanisms.
| Original language | English |
|---|---|
| Pages (from-to) | 3541-3546 |
| Number of pages | 6 |
| Journal | NeuroReport |
| Volume | 8 |
| Issue number | 16 |
| Publication status | Published - 1997 Dec 2 |
| Externally published | Yes |
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Keywords
- C-fos
- Calphostin C
- GnRH
- GT1-1
- Overexpression
- Promoter
- Protein kinase C
- Staurosporine
- TPA
ASJC Scopus subject areas
- Neuroscience(all)
Cite this
Suppression of GnRH gene expression in GT1-1 hypothalamic neuronal cells : Action of protein kinase C. / Sun, Woong; Choe, Young S.; Lee, Young J.; Kim, Kyungjin.
In: NeuroReport, Vol. 8, No. 16, 02.12.1997, p. 3541-3546.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Suppression of GnRH gene expression in GT1-1 hypothalamic neuronal cells
T2 - Action of protein kinase C
AU - Sun, Woong
AU - Choe, Young S.
AU - Lee, Young J.
AU - Kim, Kyungjin
PY - 1997/12/2
Y1 - 1997/12/2
N2 - We attempted to elucidate molecular mechanisms of gonadotropin-releasing hormone (GnRH) gene regulation by the protein kinase C (PKC) pathway in GT1- 1 cells. Activation of PKC with 12-tetra-decanoylphorbol-13-acetate (TPA) or inhibition with staurosporine or calphostin C down-regulated GnRH mRNA levels. A serial deletion mutant analysis revealed that this suppression was mediated by the proximal region (-187/-69) of the mouse GnRH promoter. TPA transiently induced c-fos mRNA, whereas staurosporine or calphostin C failed to do so. However, PKC inhibitors blocked the TPA-evoked c-fos induction. Over-expression of PKCα down-regulated GnRH promoter activity, indicating that PKC activation was sufficient to inhibit GnRH gene expression. These results suggest that both activation and inhibition of PKC decrease the GnRH gene expression in the GT1-1 cells probably through different signal cascade mechanisms.
AB - We attempted to elucidate molecular mechanisms of gonadotropin-releasing hormone (GnRH) gene regulation by the protein kinase C (PKC) pathway in GT1- 1 cells. Activation of PKC with 12-tetra-decanoylphorbol-13-acetate (TPA) or inhibition with staurosporine or calphostin C down-regulated GnRH mRNA levels. A serial deletion mutant analysis revealed that this suppression was mediated by the proximal region (-187/-69) of the mouse GnRH promoter. TPA transiently induced c-fos mRNA, whereas staurosporine or calphostin C failed to do so. However, PKC inhibitors blocked the TPA-evoked c-fos induction. Over-expression of PKCα down-regulated GnRH promoter activity, indicating that PKC activation was sufficient to inhibit GnRH gene expression. These results suggest that both activation and inhibition of PKC decrease the GnRH gene expression in the GT1-1 cells probably through different signal cascade mechanisms.
KW - C-fos
KW - Calphostin C
KW - GnRH
KW - GT1-1
KW - Overexpression
KW - Promoter
KW - Protein kinase C
KW - Staurosporine
KW - TPA
UR - http://www.scopus.com/inward/record.url?scp=0030697543&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=0030697543&partnerID=8YFLogxK
M3 - Article
C2 - 9427323
AN - SCOPUS:0030697543
VL - 8
SP - 3541
EP - 3546
JO - NeuroReport
JF - NeuroReport
SN - 0959-4965
IS - 16
ER -