In males, androgens are mainly produced by Leydig cells from the testis. A critical and highly regulated step of steroidogenesis involves the importation of cholesterol within the mitochondria by the steroidogenic acute regulatory (STAR) protein. During aging, STAR protein levels in Leydig cells gradually decrease, leading to a reduced entry of cholesterol into mitochondria and lower testosterone production. In addition to preserving its steroidogenic capacity, tumor Leydig cells can also be excellent models for evaluating the mechanisms of action of anticancer agents. In this study, we examined whether polyphenolics having structural similarities to luteolin could promote steroidogenic and cancer-related gene expressions within rat L540 tumor Leydig cells. In this cell model, luteolin activated Star expression and increased progesterone as well as testosterone productions. Interestingly, luteolin decreased gene expression related to cholesterol biosynthesis, possibly inhibiting membrane synthesis and cell proliferation. In addition, increased expression of genes such as Fas, Cdkn1a, Atp7b, and Tp53, as well as increased accumulation of cleaved caspase 3 and PARP, in response to luteolin treatment indicates that apoptosis is being activated. Luteolin also modulated the expression of genes involved in stress response, such as glutathione-S transferases Gsta1 and Gstt2, and the unfolded protein response. Thus, dietary luteolin may be effective in Leydig cell tumor chemoprevention and in maintaining steroidogenesis in aging males.

中文翻译：

---

木犀草素调节大鼠LC540肿瘤Leydig细胞中与类固醇生成，凋亡和应激反应相关的基因表达。

在雄性中，雄激素主要由睾丸的睾丸间质细胞产生。类固醇生成的关键且高度受控的步骤涉及通过类固醇生成的急性调节（STAR）蛋白在线粒体内导入胆固醇。在衰老过程中，Leydig细胞中的STAR蛋白水平逐渐降低，从而导致胆固醇进入线粒体的数量减少，睾丸激素生成降低。除了保留其类固醇生成能力外，肿瘤Leydig细胞也可以是评估抗癌药作用机理的出色模型。在这项研究中，我们检查了与木犀草素具有结构相似性的多酚类化合物是否可以促进大鼠L540肿瘤Leydig细胞内类固醇生成和癌症相关基因的表达。在这种细胞模型中，木犀草素激活星表达和增加的孕酮以及睾丸激素的生产。有趣的是，木犀草素降低了与胆固醇生物合成有关的基因表达，可能抑制了膜的合成和细胞的增殖。此外，增加的基因，如表达的Fas，CDKN1A，ATP7B，和TP53，以及裂解的caspase 3和PARP的积累增加，响应于木犀草素治疗表明凋亡被激活。木犀草素还调节与应激反应有关的基因的表达，例如谷胱甘肽-S转移酶Gsta1和Gstt2，以及展开的蛋白质反应。因此，饮食中的木犀草素可能在Leydig细胞肿瘤的化学预防和维持老年男性的类固醇生成方面有效。