3β-Hydroxysteroid dehydrogenase isoforms in human aldosterone-producing adenoma.
3β-Hydroxysteroid dehydrogenase isoforms in human aldosterone-producing adenoma.
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DOI：
10.1016/j.mce.2014.10.008
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发表时间：
2015-06-15
影响因子：
4.1
通讯作者：
Sasano H
中科院分区：
文献类型：
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作者：
Konosu-Fukaya S;Nakamura Y;Satoh F;Felizola SJ;Maekawa T;Ono Y;Morimoto R;Ise K;Takeda K;Katsu K;Fujishima F;Kasajima A;Watanabe M;Arai Y;Gomez-Sanchez EP;Gomez-Sanchez CE;Doi M;Okamura H;Sasano H
3羟类固醇脱氢酶1亚型(β-HSD3B1)和3羟类固醇脱氢酶2(HSD3B2)亚型在醛固酮腺瘤中的作用已成为一个重要的研究课题。在本研究中，我们分别用实时定量聚合酶链式反应(QPCR)和免疫组织化学方法研究了67例APA和100例APA。定量聚合酶链式反应分析结果显示，HSD3B1mRNA的丰度显著高于HSD3B1mRNA(P<；0.0001)，但仅HSD3B1mRNA与患者的醛固酮合成酶活性(P<；0.0001)和血浆醛固酮浓度(P<；0.0001)显著相关。免疫组织化学结果显示，HSD3B2在绝大多数APA中呈阳性表达，但HSD3B1与细胞色素P11B2之间也存在显着相关性(P<；0.0001)。在KCNJ5突变的APA中，CYP11B2mRNA(P<0.0001)和HSD3B1mRNA(P=0.011)显著高于野生型APA。这些结果表明，尽管HSD3B1的表达水平低于HSD3B2，但它参与了醛固酮的产生，并可能与APA的KCNJ5突变有关。
It has become important to evaluate the possible involvement of 3β-hydroxysteroid dehydrogenase type 1 (HSD3B1) and 2 (HSD3B2) isoforms in aldosterone-producing adenoma (APA). In this study, we studied 67 and 100 APA cases using real-time quantitative PCR (qPCR) and immunohistochemistry, respectively. Results of qPCR analysis demonstrated that HSD3B2 mRNA was significantly more abundant than HSD3B1 mRNA (P < 0.0001), but only HSD3B1 mRNA significantly correlated with CYP11B2 (aldosterone synthase) mRNA (P < 0.0001) and plasma aldosterone concentration (PAC) of the patients (P < 0.0001). Results of immunohistochemistry subsequently revealed that HSD3B2 immunoreactivity was detected in the great majority of APA but a significant correlation was also detected between HSD3B1 and CYP11B2 (P < 0.0001). In KCNJ5 mutated APA, CYP11B2 mRNA (P < 0.0001) and HSD3B1 mRNA (P = 0.011) were significantly higher than those of wild type APA. These results suggest that HSD3B1 is involved in aldosterone production, despite its lower levels of expression compared with HSD3B2, and also possibly associated with KCNJ5 mutation in APA.