Travert Carine, Carreau Serge, Le Goff Dominique
Biochemistry Laboratory EA 2608-USC INRA 2006, IBFA, University of Caen, Esplanade de la Paix, 14302 Caen Cedex, France.
Reprod Toxicol. 2006 Nov;22(4):564-70. doi: 10.1016/j.reprotox.2006.05.006. Epub 2006 May 22.
Testicular macrophages can convert cholesterol into 25-hydroxycholesterol which strongly stimulates Leydig cell testosterone production. We demonstrated that 25-hydroxycholesterol reduced cholesterol biosynthesis in adult rat Leydig cells. This oxysterol can also be cytotoxic. As hydroxylated cholesterol can induce apoptosis in various cells, we investigated cell death produced by 25-hydroxycholesterol. Apoptosis was characterized by TUNEL assay and by DAPI test. Addition of 25-hydroxycholesterol, during 24h, induced a dose dependent increase of apoptosis. This effect was reduced by a treatment with a caspase-3 inhibitor (Ac-DEVD-CHO). 25-Hydroxycholesterol is known to stimulate testosterone production, but an increase of intracellular or culture medium testosterone level does not modify significantly the percentage of apoptotic cells. In contrast, addition of 17beta-estradiol (2 nM) induced a decrease of apoptotic cells. These data suggested that this oxysterol can be used by rat Leydig cells in culture for sterol metabolism, but also induces apoptosis which could be inhibited by 17beta-estradiol.
睾丸巨噬细胞可将胆固醇转化为25-羟胆固醇，后者能强烈刺激睾丸间质细胞产生睾酮。我们证明，25-羟胆固醇可降低成年大鼠睾丸间质细胞中的胆固醇生物合成。这种氧化甾醇也具有细胞毒性。由于羟基化胆固醇可诱导多种细胞凋亡，我们研究了25-羟胆固醇所导致的细胞死亡。通过TUNEL检测法和DAPI检测法对细胞凋亡进行了表征。在24小时内添加25-羟胆固醇可诱导凋亡呈剂量依赖性增加。用半胱天冬酶-3抑制剂（Ac-DEVD-CHO）处理可降低这种效应。已知25-羟胆固醇可刺激睾酮生成，但细胞内或培养基中睾酮水平的升高并不会显著改变凋亡细胞的百分比。相反，添加17β-雌二醇（2 nM）可诱导凋亡细胞减少。这些数据表明，这种氧化甾醇可被培养的大鼠睾丸间质细胞用于甾醇代谢，但也会诱导凋亡，而17β-雌二醇可抑制这种凋亡。
