Insulin-like growth factor-I is an important antiapoptotic factor for rat Leydig cells during postnatal development
Insulin-like growth factor-I is an important antiapoptotic factor for rat Leydig cells during postnatal development
复制标题
DOI：
10.1210/en.2006-0835
复制
发表时间：
2007-01-01
期刊：
影响因子：
4.8
通讯作者：
Soder, Olle
中科院分区：
文献类型：
--
作者：
Colon, Eugenia;Zaman, Farasat;Soder, Olle
本研究探讨了 IGF-I 的影响以及 IGF-I 受体 (IGF-IR) 在 Leydig 细胞凋亡/存活中的作用。对不同年龄大鼠睾丸的免疫组织化学分析显示，磷酸化IGF-IR的水平从出生到出生后第20天增加，在成年睾丸中保持较高水平。蛋白质印迹显示，从 40 日龄大鼠中分离的 Leydig 细胞中的这一水平高于从 10 日龄或 60 日龄大鼠中分离的细胞。应用末端脱氧核糖核苷酸转移酶介导的脱氧尿苷三磷酸缺口末端标记测定表明，IGF-I 可降低所有发育阶段 Leydig 细胞的凋亡水平，而 IGF-IR 的选择性抑制剂鬼臼苦素可阻断这种抗凋亡作用。 IGF-I 抗凋亡作用的机制涉及磷脂酰肌醇 3-激酶/Akt 途径，在未成熟的 Leydig 细胞中，该生长因子增强 Bcl-2 和细胞凋亡蛋白 2 细胞抑制剂的表达，同时防止通过裂解激活 caspase-3。此外，IGF-II 和高浓度的胰岛素也会引起 IGF-IR 的磷酸化，并且与 IGF-I 一样，增强 Leydig 细胞的类固醇生成急性调节蛋白的表达。无论存在还是不存在 IGF-I，鬼臼苦素对 IGF-IR 的抑制都会降低 Leydig 细胞的存活率，这表明通过 IGF-IR 的信号传导在 Leydig 细胞存活中发挥着重要作用。
The present investigation examines the influence of IGF-I and the role of IGF-I receptor ( IGF-IR) in the apoptosis/survival of Leydig cells. Immunohistochemical analysis of the rat testis at different ages revealed that the level of the phosphorylated IGF-IR increases from birth to d20 of postnatal life, remaining high in the adult testis. Western blotting revealed that this level is higher in Leydig cells isolated from 40-d-old than from 10- or 60-d-old rats. Application of the terminal deoxyribonucleotidyl transferase-mediated deoxyuridine triphosphate nick end labeling assay revealed that IGF-I decreases the level of apoptosis in Leydig cells at all stages of development, and the selective inhibitor of IGF-IR, picropodophyllin, blocks this antiapoptotic effect. The mechanism underlying the antiapoptotic action of IGF-I involves the phosphatidylinositol 3-kinase/Akt pathway, and in immature Leydig cells, this growth factor enhances the expression of Bcl-2 and cellular inhibitor of apoptosis proteins 2, while preventing activation of caspase-3 by cleavage. Furthermore, IGF-II and high concentrations of insulin also evoke phosphorylation of IGF-IR and, like IGF-I, enhance the expression of the steroidogenic acute regulatory protein by Leydig cells. Inhibition of IGF-IR by picropodophyllin decreases the survival of Leydig cells, both in the presence and absence of IGF-I, demonstrating that signaling via the IGF-IR plays an important role in Leydig cell survival.