The novel angiotensin-converting enzyme (ACE) homolog, ACE2, is selectively expressed by adult Leydig cells of the testis
The novel angiotensin-converting enzyme (ACE) homolog, ACE2, is selectively expressed by adult Leydig cells of the testis
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DOI：
10.1210/en.2004-0443
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发表时间：
2004-10-01
期刊：
影响因子：
4.8
通讯作者：
Lew, RA
中科院分区：
文献类型：
--
作者：
Douglas, GC;O'Bryan, MK;Lew, RA
金属肽酶血管紧张素转换酶（ACE）通过产生血管收缩肽血管紧张素II在心血管系统中起关键作用。具有不同底物特异性的ACE同源物ACE 2最近被克隆，其表现出仅限于心脏和肾脏的内皮细胞、肾脏远端小管的上皮细胞和睾丸的表达模式。虽然ACE 2对心脏功能的重要性已经很明显，但其在睾丸中的作用仍然未知。在这项研究中，我们报告了人睾丸ACE 2的克隆和表达，并确认它是相同的体细胞形式的酶。ACE 2催化活性存在于成年大鼠的整个睾丸和间质细胞的膜制备物中;蛋白质在间质细胞中的表达通过Western免疫印迹分析得到证实。使用免疫组织化学，ACE 2表达仅限于大鼠睾丸间质细胞和人睾丸间质细胞和支持细胞。用特异性毒素乙烷二甲烷磺酸盐（ethane dimethane sulfonate）消融大鼠睾丸间质细胞，可消除睾丸组织中的ACE 2阳性细胞。ACE 2在大鼠Leydig细胞中的表达在青春期和乙烷二甲烷磺酸处理后的成年型Leydig细胞的发育过程中上调。睾丸中ACE 2活性的表达没有显着改变的垂体-睾丸激素轴与SC睾酮植入物的操作。这些数据表明，ACE 2是一个组成型的睾丸间质细胞的产品，并可能参与控制睾丸功能的机制还不清楚。
The metallopeptidase angiotensin-converting enzyme (ACE) plays a pivotal role in the cardiovascular system by generating the vasoconstrictor peptide angiotensin II. A homolog of ACE with different substrate specificity, ACE2, has recently been cloned that shows an expression pattern restricted to endothelial cells of the heart and kidney, epithelial cells of the distal tubule of the kidney, and the testis. Although the importance of ACE2 to cardiac function is already evident, its role in the testis remains unknown. In this study, we report the cloning and expression of human testicular ACE2 and confirm that it is identical to the somatic form of the enzyme. ACE2 catalytic activity was present in membrane preparations of whole testes and Leydig cells from adult rats; expression of the protein in Leydig cells was confirmed by Western immunoblot analysis. Using immunohistochemistry, ACE2 expression was confined to the Leydig cells in the rat testis and to Leydig and Sertoli cells in the human testis. Ablation of the Leydig cells in the rat by the specific toxin, ethane dimethane sulfonate, eliminated ACE2-positive cells from the interstitium. Expression of ACE2 in rat Leydig cells was up-regulated during the development of adult-type Leydig cells at puberty and after ethane dimethane sulfonate treatment. Expression of ACE2 activity in the testis was not significantly altered by manipulation of the pituitary-testicular hormonal axis with sc testosterone implants. These data suggest that ACE2 is a constitutive product of adult-type Leydig cells and may participate in the control of testicular function by as yet unknown mechanisms.