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促肾上腺皮质激素(ACTH)和佛波酯刺激人产生皮质醇的肾上腺腺瘤中蛋白激酶C的重新分布。

ACTH and phorbol ester stimulated redistribution of protein kinase C in human cortisol-producing adrenal adenoma.

作者信息

Kajita K, Ishizuka T, Yamamoto M, Nagashima T, Taniguchi O, Mune T, Murayama M, Kitagawa S, Yasuda K

机构信息

Nagahama Red Cross Hospital, Shiga, Japan.

出版信息

Endocr J. 1994 Feb;41(1):107-13. doi: 10.1507/endocrj.41.107.

Abstract

We studied the steroidogenetic action and concomitant subcellular redistribution of protein kinase C (PKC) in cortisol hypersecreting adrenal adenoma cells obtained from two patients with Cushing's syndrome. Isolated adenoma cells were treated with 10(-9) M and 10(-6) M 12-O-tetradecanoyl phorbol-13-acetate (TPA) or 10(-6) M ACTH. Treatment of the isolated adenoma cells with TPA resulted in cortisol secretion equivalent to that with ACTH-treatment. Immunoblot analysis of PKC during treatment with ACTH or TPA showed that PKC beta translocated from cytosol to membrane. A small amount of PKC alpha, but not membrane-associated PKC alpha, was detectable in the cytosolic fraction. It appeared that TPA-induced cortisol secretion mimicked ACTH-induced cortisol secretion, and that PKC beta translocated from cytosol to membrane on stimulation by both ACTH and TPA. We suggested that ACTH-induced cortisol secretion in human cortisol hypersecreting adrenal adenoma is mediated by PKC beta activation.

摘要

我们研究了从两名库欣综合征患者获取的皮质醇分泌过多的肾上腺腺瘤细胞中蛋白激酶C(PKC)的类固醇生成作用及伴随的亚细胞重新分布。分离出的腺瘤细胞用10⁻⁹ M和10⁻⁶ M的12 - O - 十四酰佛波醇 - 13 - 乙酸酯(TPA)或10⁻⁶ M促肾上腺皮质激素(ACTH)处理。用TPA处理分离出的腺瘤细胞导致皮质醇分泌量与用ACTH处理相当。对用ACTH或TPA处理期间的PKC进行免疫印迹分析表明,PKCβ从胞质溶胶转位到细胞膜。在胞质溶胶部分可检测到少量的PKCα,但未检测到与膜相关的PKCα。似乎TPA诱导的皮质醇分泌模拟了ACTH诱导的皮质醇分泌,并且在ACTH和TPA刺激下PKCβ均从胞质溶胶转位到细胞膜。我们认为,人皮质醇分泌过多的肾上腺腺瘤中ACTH诱导的皮质醇分泌是由PKCβ激活介导的。

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