Differential regulation of 3beta-hydroxysteroid dehydrogenase type II and 17alpha-hydroxylase/lyase P450 in human adrenocortical carcinoma cells by epidermal growth factor and basic fibroblast growth factor.

Differential regulation of 3beta-hydroxysteroid dehydrogenase type II and 17alpha-hydroxylase/lyase P450 in human adrenocortical carcinoma cells by epidermal growth factor and basic fibroblast growth factor.
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表皮生长因子和碱性成纤维细胞生长因子对人肾上腺皮质癌细胞中 3β-羟基类固醇脱氢酶 II 型和 17α-羟化酶/裂解酶 P450 的差异调节。

DOI:
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发表时间:
2001
影响因子:
4
通讯作者:
Mitsuhiro Okamoto
Mitsuhiro Okamoto
中科院分区:
医学2区
文献类型:
--
作者:
J. Doi;H. Takemori;M. Ohta;Y. Nonaka;Mitsuhiro Okamoto

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表皮生长因子(EGF)和碱性成纤维细胞生长因子(bFGF)是刺激肾上腺皮质细胞增殖和类固醇生成的多能生长因子。本研究表明,EGF和bFGF在人肾上腺皮质H295R细胞中特异性诱导3β -羟基类固醇脱氢酶II型(3betaHSD II) mRNA表达,并抑制17α -羟化酶/裂解酶P450 (CYP17) mRNA表达。3betaHSD II mRNA的诱导直到生长因子处理后6小时才发生,并且在蛋白质合成抑制剂环己亚胺(CHX)存在下被完全消除,这表明诱导需要从头合成蛋白质。CYP17 mRNA的抑制几乎与3betaHSD II mRNA的诱导同时开始。有趣的是,CYP17 mRNA水平在CHX处理后升高。3betaHSD II和CYP17 mrna均被钙调蛋白激酶II (CaMK II)抑制剂KN-93抑制,而被丝裂原活化蛋白激酶(MAPK)抑制剂PD98059增强。pd98059介导的3betaHSD II mRNA的诱导被CHX处理完全阻断。有趣的是,在PD98059和CHX同时存在的情况下,EGF治疗比单独存在PD98059的治疗产生了更大的CYP17 mRNA的增加。这些结果表明chx敏感因子(s)和CaMK II-和mapk -信号通路可能在H295R细胞中EGF或bFGF诱导3betaHSD II和抑制CYP17中发挥重要作用。
Epidermal growth factor (EGF) and basic fibroblast growth factor (bFGF) are pluripotent growth factors that stimulate both the proliferation and steroidogenesis of adrenocortical cells. Here we demonstrate that EGF and bFGF specifically induce mRNA of 3beta-hydroxysteroid dehydrogenase type II (3betaHSD II) and suppress that of 17alpha-hydroxylase/lyase P450 (CYP17) in human adrenocortical H295R cells. The induction of 3betaHSD II mRNA did not occur until 6 h after the growth factor treatment and was completely abolished in the presence of a protein synthesis inhibitor, cycloheximide (CHX), suggesting that the induction required de novo protein synthesis. The CYP17 mRNA suppression began at almost the same time as the induction of the 3betaHSD II mRNA. Interestingly, the CYP17 mRNA level was increased by the CHX treatment. Both the 3betaHSD II and CYP17 mRNAs were repressed by treatment with a calmodulin kinase II (CaMK II) inhibitor, KN-93, and were enhanced by a mitogen-activated protein kinase (MAPK) inhibitor, PD98059. The PD98059-mediated induction of the 3betaHSD II mRNA was completely blocked by the CHX treatment. Interestingly, treatment with EGF in the presence of both PD98059 and CHX produced a greater increase in the CYP17 mRNA than did treatment in the presence of PD98059 alone. These results suggest that CHX-sensitive factor(s) and CaMK II- and MAPK-signaling pathways may have important roles in both induction of 3betaHSD II and suppression of CYP17 by EGF or bFGF in H295R cells.
人肾上腺皮质 H295R 细胞中 3β-羟基类固醇脱氢酶表达的调节。
DOI: --
发表时间: 1996
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影响因子: --
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