Regulation of steroid hormone biosynthesis enzymes and organic anion transporters by forskolin and DHEA-S treatment in adrenocortical cells
Regulation of steroid hormone biosynthesis enzymes and organic anion transporters by forskolin and DHEA-S treatment in adrenocortical cells
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DOI：
10.1152/ajpendo.00653.2005
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发表时间：
2006-12-01
影响因子：
5.1
通讯作者：
Hagos, Yohannes
中科院分区：
文献类型：
--
作者：
Asif, Abdul R.;Ljubojevic, Marija;Hagos, Yohannes
forskolin和DHEA-S处理对肾上腺皮质细胞中类固醇激素生物合成酶和有机阴离子转运蛋白的调控。[J] .中国生物医学工程学报，2009,31(2):559 - 559。首次出版于2006年7月11日；doi: 10.1152 / ajpendo.00653.2005。一些重要的生理功能是由皮质醇调节的。先前，我们证实了人类有机阴离子转运蛋白3 （hOAT3）参与皮质醇释放。在本研究中，我们研究了硫酸脱氢表雄酮（DHEA-S）和硫酸雌酮对人肾上腺皮质细胞系（NCI-H295R）皮质醇释放的影响，并与福斯克林刺激进行了比较。此外，我们还检测了forskolin和DHEA-S对NCI-H295R细胞中类固醇生物合成关键酶表达以及hOAT3和-4表达的影响。与DHEA-S孵育24小时后，皮质醇的释放量增加了10倍，但与硫酸雌酮孵育没有显示出皮质醇释放的任何显著变化。当细胞与DHEA-S在forskolin存在下孵育时，DHEA-S刺激皮质醇的累加性影响比单独的forskolin记录。用forskolin刺激NCI-H295R细胞24小时后，类固醇急性调节蛋白（StAR）、CYP17、CYP21A2和CYP11A1的表达增加，而DHEA-S孵育后，只有StAR mRNA的表达显著增加。免疫荧光分析显示，foskolin和DHEA-S刺激显著提高了hOAT3的表达。我们认为，DHEA-S和forskolin刺激下肾上腺皮质细胞皮质醇释放增加可能与类固醇生物合成关键酶和hOAT3的高表达有关。
Regulation of steroid hormone biosynthesis enzymes and organic anion transporters by forskolin and DHEA-S treatment in adrenocortical cells. Am J Physiol Endocrinol Metab 291:E1351-E1359, 2006. First published July 11, 2006; doi:10.1152/ajpendo.00653.2005.-Several important physiological functions are regulated by cortisol. Previously, we demonstrated the involvement of human organic anion transporter 3 (hOAT3) in cortisol release. In the present study, we investigated the influence of dehydroepiandrosterone sulfate (DHEA-S) and estrone sulfate on cortisol release in a human adrenocortical cell line (NCI-H295R) compared with forskolin stimulation. Additionally, we examined the impact of forskolin and DHEA-S on the expression of key enzymes in steroid biosynthesis and expression of hOAT3 and -4 in NCI-H295R cells. The cortisol release was increased 10-fold after 24-h incubation with DHEA-S, but incubation with estrone sulfate did not show any significant change in cortisol release. When cells were incubated with DHEA-S in the presence of forskolin, an additive influence of DHEA-S stimulation of cortisol was recorded over forskolin alone. The 24-h stimulation of NCI-H295R cells with forskolin increased the expression of steroidogenic acute regulatory protein ( StAR), CYP17, CYP21A2, and CYP11A1, whereas only StAR mRNA expression was increased significantly by incubation with DHEA-S. Immunofluorescence analyses revealed strongly elevated expression of hOAT3 by forskolin as well as by DHEA-S stimulation. We conclude that the increased cortisol release of adrenocortical cells by DHEA-S and forskolin stimulation is probably due to high expression of the key enzymes of steroid biosynthesis and hOAT3.