ACTH and AII differentially stimulate steroid hormone orphan receptor mRNAs in adrenal cortical cells
ACTH and AII differentially stimulate steroid hormone orphan receptor mRNAs in adrenal cortical cells
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DOI：
10.1016/s0303-7207(96)03938-x
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发表时间：
1996-11-29
影响因子：
4.1
通讯作者：
Enyeart, JA
中科院分区：
文献类型：
--
作者：
Enyeart, JJ;Boyd, RT;Enyeart, JA
NGFI-B和Ad 4 BP是类固醇激素受体样转录因子，可以控制肾上腺皮质中的类固醇生成、生长和分化。我们已经研究了NGFI-B和Ad 4 BP mRNA的诱导肽激素，ACTH，AII，IGF，FGF，和KCl去极化培养的牛肾上腺皮质细胞。这两个转录因子的mRNA是最有效的，但差异诱导ACTH和AII。NGFI-B的mRNA在未刺激的细胞中通常检测不到，但在对ACTH和AII的反应中迅速（< 30分钟）积累。峰值增加发生在2-3 h内，之后mRNA水平下降。在最大有效浓度下，AII产生的NGFI-B mRNA增加比ACTH（n = 7）触发的增加大2.7倍。与NGFI-B相反，Ad 4 BP mRNA在未刺激的细胞中容易检测到。ACTH和AII诱导的Ad 4 BP mRNA的增加更小、更慢和更持续。Ad 4 BP mRNA在6- 8h达高峰，持续升高至少18 h。促肾上腺皮质激素产生的Ad 4 BP的增加是2.6倍大于刺激AII（n = 8）。将ACTH和AII受体与皮质醇分泌偶联的主要信号通路的拮抗剂，包括T型Ca 2+拮抗剂Ni 2+和五氟利多、CaM激酶拮抗剂KN-62、A激酶拮抗剂H-89和非选择性激酶拮抗剂星形孢菌素，都未能抑制由这两种肽触发的NGFI-B和Ad 4 BP mRNA的增加。这些药物中的每一种都有效地抑制了由肽刺激的皮质醇产生。此外，反对他们提出的类固醇生成酶的转录因子的作用，ACTH和AII刺激的类固醇孤儿受体mRNA的增加与皮质醇产生的相应增加在24小时内测量不相关。结果表明，NGFI-B和Ad 4 BP mRNA的差异调节ACTH和AII。只有NGFI-B是快速和短暂增加的动力学常见的立即早期基因。肽刺激孤儿受体mRNA的增加和皮质醇的产生之间缺乏相关性，与相关信号通路的明显分歧相结合，反对这些转录因子在ACTH和AII刺激的类固醇生成中的主要作用。这些肽类激素作为发育和皮质类固醇合成的介质的双重功能可能需要单独的平行信号通路的存在。版权所有（C）1996 Elsevier Science爱尔兰有限公司
NGFI-B and Ad4BP are steroid hormone receptor-like transcription factors that may control steroidogenesis, growth and differentiation in the adrenal cortex. We have studied-the induction of NGFI-B and Ad4BP mRNAs by the peptide hormones, ACTH, AII, IGF, FGF, and by KCl depolarization in cultured bovine adrenocortical cells. The mRNAs for these two transcription factors were most effectively but differentially induced by ACTH and AII. mRNA for NGFI-B was,typically undetectable in unstimulated cells, but rapidly (< 30 min) accumulated in response to ACTH and AII. Peak increases occurred within 2-3 h after which mRNA levels declined. At maximally effective concentrations, AII produced increases in NGFI-B mRNA 2.7-fold larger than those triggered by ACTH (n = 7). In contrast to NGFI-B, Ad4BP mRNA was readily detectable in unstimulated cells. ACTH and AII induced smaller, slower and more sustained increases in Ad4BP mRNA. peak values were obtained in 6-8 h and Ad4BP mRNA remained elevated for at least 18 h. ACTH produced increases in Ad4BP that were 2.6-fold larger than those stimulated by AII (n = 8). Antagonists of major signaling pathways that couple ACTH and AII receptors to cortisol secretion, including T-type Ca2+ antagonists Ni2+ and penfluridol, the CaM kinase antagonist KN-62, the A-kinase antagonist H-89 and the non-selective kinase antagonist staurosporine, all failed to suppress increases in NGFI-B and Ad4BP mRNAs triggered by these two peptides. Each of these agents effectively inhibited cortisol production stimulated by the peptides. Further, arguing against their proposed role as transcription factors' for steroidogenic enzymes, ACTH- and AII-stimulated increases in steroid orphan receptor mRNAs were not correlated with corresponding increases in cortisol production measured over 24 h. The results show that NGFI-B and Ad4BP mRNAs are differentially regulated by ACTH and AII. Only NGFI-B is rapidly and transiently increased with kinetics common to immediate early genes. The lack of correlation between peptide-stimulated increases in orphan receptor mRNAs and cortisol production in combination with the apparent divergence in the associated signaling pathways argue against a primary role for these transcription factors in ACTH- and AII-stimulated steroidogenesis. The dual function of these peptide hormones as mediators of development and corticosteroid synthesis could necessitate the presence of separate, parallel signaling pathways. Copyright (C) 1996 Elsevier Science Ireland Ltd.