Regulation of Lhb and Egr1 gene expression by GNRH pulses in rat pituitaries is both c-Jun N-terminal kinase (JNK)- and extracellular signal-regulated kinase (ERK)-dependent.
Regulation of Lhb and Egr1 gene expression by GNRH pulses in rat pituitaries is both c-Jun N-terminal kinase (JNK)- and extracellular signal-regulated kinase (ERK)-dependent.
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DOI：
10.1095/biolreprod.109.079426
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发表时间：
2009-12
影响因子：
3.6
通讯作者：
Marshall JC
中科院分区：
文献类型：
--
作者：
Burger LL;Haisenleder DJ;Aylor KW;Marshall JC
脉冲式GNRH以不同的方式调节促性腺激素亚基基因，更快的频率有利于Lhb基因表达，而更慢的频率有利于Fshb基因表达。早期生长反应1（EGR 1）是Lhb基因转录的关键。我们在体内和培养的大鼠垂体细胞中研究了GnRH对EGR 1及其两种共阻遏物Ngfi-A结合蛋白1和2（NAB 1和NAB 2）的调节。在大鼠中，快速GNRH脉冲（每30 min）诱导Egr 1初级转录物（PT）和mRNA稳定地增加2倍（p<0.05），持续1- 24 h。相反，缓慢的GNRH脉冲（每240分钟）在24小时增加Egr 1 PT（6倍; p<0.05），但在4和24小时之间增加Egr 1 mRNA 4-5倍。两种GNRH脉冲频率均使EGR 1蛋白增加3-4倍。在培养的大鼠垂体细胞中，GNRH脉冲（每60分钟）增加Egr 1（PT = 2.5-3倍; mRNA = 1.5-2倍; p<0.05）。无论在体内还是体外，GNRH脉冲对Nab 1/2 PT/mRNA的影响都很小。我们还研究了特定的细胞内信号级联激活的GNRH。丝裂原活化蛋白激酶8/9（MAPK 8/9 [aka JNK]; SP 600125）和MAP激酶激酶1（MAP 2K 1 [aka MEK 1]; PD 98059）抑制剂减弱或完全抑制了Lhb PT和Egr 1 PT/mRNA的GNRH诱导，而MAPK 14（aka p38）抑制剂SB 203580则没有。总之，脉冲GNRH刺激Egr 1基因表达和蛋白在体内，但不是以频率依赖性的方式。此外，GNRH诱导的Egr 1基因表达是由MAPK 8/9和MAPK 1/3介导的，这两个蛋白对Lhb基因的转录都是至关重要的。
Pulsatile GNRH regulates the gonadotropin subunit genes in a differential manner, with faster frequencies favoring Lhb gene expression and slower favoring Fshb. Early growth response 1 (EGR1) is critical for Lhb gene transcription. We examined GNRH regulation of EGR1, and its two co-repressors Ngfi-A binding proteins 1 and 2 (NAB1 and NAB2), both in vivo and in cultured rat pituitary cells. In rats, fast GNRH pulses (every 30min) induced Egr1 primary transcript (PT) and mRNA stably 2-fold (p<0.05) for 1–24h. In contrast slow GNRH pulses (every 240min) increased Egr1 PT at 24h (6-fold; p<0.05), but increased Egr1 mRNA 4–5 fold between 4 and 24h. Both GNRH pulse frequencies increased EGR1 protein 3–4 fold. In cultured rat pituitary cells, GNRH pulses (every 60min) increased Egr1 (PT = 2.5–3 fold; mRNA = 1.5–2 fold; p<0.05). GNRH pulses had little effect on Nab1/2 PT/mRNAs either in vivo or in vitro. We also examined specific intracellular signaling cascades activated by GNRH. Inhibitors of Mitogen Activated Protein Kinases 8/9 (MAPK8/9 [aka JNK]; SP600125) and MAP Kinase Kinase 1 (MAP2K1 [aka MEK1]; PD98059) either blunted or totally suppressed the GNRH induction of Lhb PT and Egr1 PT/mRNA, whereas the MAPK14 (aka p38) inhibitor SB203580 did not. In summary, pulsatile GNRH stimulates Egr1 gene expression and protein in vivo, but not in a frequency dependent manner. Additionally, GNRH induced Egr1 gene expression is mediated by MAPK8/9 and MAPK1/3, and both are critical for Lhb gene transcription.
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影响因子：
4.1
作者：
Dobkin-Bekman, Masha;Naidich, Michal;Naor, Zvi
通讯作者：
Naor, Zvi
影响因子：
20.3
作者：
Gururajan, M;Chui, R;Bondada, S
通讯作者：
Bondada, S
影响因子：
4.8
作者：
Haisenleder, D. J.;Burger, L. L.;Marshall, J. C.
通讯作者：
Marshall, J. C.
影响因子：
3.6
作者：
Ferris, Heather A.;Walsh, Heidi E.;Shupnik, Margaret A.
通讯作者：
Shupnik, Margaret A.
影响因子：
4.1
作者：
CLAYTON, RN;LALLOZ, MRA;ROBERTS, JL
通讯作者：
ROBERTS, JL