Molecular diversity of 11β-HSDs involved in a protection mechanism from the stress-mediated suppression of testosterone production

11β-HSD 的分子多样性参与应激介导的睾酮产生抑制的保护机制

• 批准号: 20590125
• 负责人: NAKAJIN Shizuo
• 金额: $ 2.25万
• 依托单位: Hoshi University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 2008
• 资助国家: 日本
• 起止时间: 2008 至 2010
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-20590125/
• 关键词: ストレス; テストステロン; 精巣; ライディッヒ細胞; 精子形成; 11β-HSD; 分子多様性; アイソザイム

11β-Hydroxysteroid dehydrogenase (11β-HSD) isozyme (type 1 and type 2) catalyze the interconversion of physiologically active GC and inactive forms. The presence of these isozymes was determined in neonatal pig testis and Leydig cells purified from testes by RT-PCR, Western blotting, and immunohistochemical staining. In the entire testis, a higher level of type 2 was expressed compared to type 1. Next, the direction of GC metabolism in intact Leydig cells was examined, and only oxidation from cortisol to cortisone was detected. Using a microsomal enzyme preparation from Leydig cells, type 2 exhibited potent oxidation activity, and the activity was higher than the oxidation activity catalyzed by the type 1 isozyme. Furthermore, we performed comprehensive determination of the expression of 11β-HSD isozymes mRNA by real-time RT-PCR in wide range of human tissues. The results of the present study using testis strongly suggest that not only 11β-HSD type 1 but also type 2 plays important roles in cortisol inactivation in Leydig cells of the testis, and is involved in the protection of glucocorticoid -mediated suppression of testosterone production in Leydig cells of the testis.

11β-羟基类固醇脱氢酶（11β-HSD）同工酶（1型和2型）催化生理活性GC和非活性形式的相互转化。这些同工酶的存在下，确定在新生猪睾丸和睾丸间质细胞纯化的RT-PCR，蛋白质印迹和免疫组织化学染色。在整个睾丸中，与1型相比，2型表达水平更高。接下来，在完整的Leydig细胞GC代谢的方向进行了检查，只有从皮质醇到可的松的氧化检测。使用微粒体酶制剂从Leydig细胞，2型表现出强大的氧化活性，活性高于氧化活性催化的1型同工酶。此外，我们还采用实时荧光定量RT-PCR技术对11种β-HSD同工酶mRNA在多种人体组织中的表达进行了全面的检测。本研究结果表明，11β-HSD 1型和11 β-HSD 2型在睾丸Leydig细胞皮质醇失活中均起重要作用，并参与保护睾丸Leydig细胞中糖皮质激素介导的睾酮生成抑制。

项目成果

Sequence and expression of 11β-hydroxysteroid dehydrogenase type 1 cDNA cloned from pig testis

猪睾丸11β-羟基类固醇脱氢酶1型cDNA的序列和表达

• 发表时间: 2010
• 期刊: Mol.Cell.Biochem. 338(1-2)
• 作者: S.Ohno;M.Ohta;Y.Honda;S.Nakajin
• 通讯作者: S.Nakajin

ブタ11β-HSD type 1 cDNAの新規配列とその発現

猪11β-HSD 1型cDNA新序列及其表达

• 发表时间: 2010
• 作者: 大田正規;本田容子;大野修司;中陳静男
• 通讯作者: 中陳静男

Quantitative determination and tissue distribution of human 11β-hydroxysteroid dehydrogenase, hexose-6-phosphate dehydrogenase, glucose-6-phosphate transporter, glucocorticoid receptor and mineralocorticoid receptor mRNAs, Horm.

人 11β-羟基类固醇脱氢酶、6-磷酸己糖脱氢酶、6-磷酸葡萄糖转运蛋白、糖皮质激素受体和盐皮质激素受体 mRNA 的定量测定和组织分布，Horm。

• 发表时间: 2010
• 期刊: Mol.Biol.Clin.Invest. 2(1)
• 作者: S.Ohno;M.Ohta;S.Nakajin
• 通讯作者: S.Nakajin

Quantitative determination and tissue distribution of human 11β-hydroxysteroid dehydrogenase, hexose-6-phosphate dehydrogenase, glucose-6-phosphate transporter, glucocorticoid receptor and mineral ocorticoid receptor mRNAs

人 11β-羟基类固醇脱氢酶、6-磷酸己糖脱氢酶、6-磷酸葡萄糖转运蛋白、糖皮质激素受体和盐皮质激素受体 mRNA 的定量测定和组织分布

• 发表时间: 2010
• 期刊: Horm.Mol.Biol.Clin.Invest.
• 作者: S.Ohno;M.Ohta;S.Nakajin
• 通讯作者: S.Nakajin

Leydig cells from neonatal pig testis abundantly express 11β-hydroxysteroid dehydrogenase (11β-HSD) type 2 and effectively inactivate cortisol to cortisone

• DOI: 10.1016/j.jsbmb.2007.07.003
• 发表时间: 2008-01-01
• 期刊: JOURNAL OF STEROID BIOCHEMISTRY AND MOLECULAR BIOLOGY
• 影响因子: 4.1
• 作者: Honda, Y.;Ohno, S.;Nakajin, S.
• 通讯作者: Nakajin, S.