Department of Endocrinology, Faculty of Biology, Institute of Zoology and Biomedical Research, Jagiellonian University in Krakow, 30-387, Kraków, Poland.
Center of Experimental and Innovative Medicine, University of Agriculture in Krakow, 30-248, Kraków, Poland.
Sci Rep. 2021 Jul 2;11(1):13772. doi: 10.1038/s41598-021-93292-8.
Our present knowledge on interrelation between morphology/ultrastructure of mitochondria of the Leydig cell and its steroidogenic function is far from satisfactory and needs additional studies. Here, we analyzed the effects of blockade of androgen receptor, triggered by exposure to flutamide, on the expression of steroidogenic proteins (1) and ultrastructure of Leydig cells' constituents (2). We demonstrated that increase in the expression level of steroidogenic (StAR, CYP11A1, 3β-HSD, and CYP19A1) proteins (and respective mRNAs) in rat testicular tissue as well as elevation of intratesticular sex steroid hormone (testosterone and estradiol) levels observed in treated animals correspond well to morphological alterations of the Leydig cell ultrastructure. Most importantly, up-regulation of steroidogenic proteins' expression apparently correlates with considerable multiplication of Leydig cell mitochondria and subsequent formation of local mitochondrial networks. Interestingly, we showed also that the above-mentioned processes were associated with elevated transcription of Drp1 and Mfn2 genes, encoding proteins implicated in mitochondrial dynamics. Collectively, our studies emphasize the importance of mitochondrial homeostasis to the steroidogenic function of Leydig cells.
我们目前对于睾丸间质细胞线粒体形态/超微结构与其类固醇生成功能之间的关系的了解还远远不够，需要进一步研究。在这里，我们分析了雄激素受体阻断（通过暴露于氟他胺触发）对类固醇生成蛋白表达的影响 (1) 和睾丸间质细胞成分的超微结构 (2)。我们证明，在接受治疗的动物中，睾丸组织中类固醇生成蛋白（StAR、CYP11A1、3β-HSD 和 CYP19A1）（和相应的 mRNA）的表达水平增加以及睾丸内性激素（睾丸激素和雌二醇）水平升高与睾丸间质细胞超微结构的形态改变非常吻合。最重要的是，类固醇生成蛋白表达的上调显然与睾丸间质细胞线粒体的大量增殖以及随后形成局部线粒体网络有关。有趣的是，我们还表明，上述过程与 Drp1 和 Mfn2 基因的转录升高有关，这些基因编码参与线粒体动力学的蛋白质。总之，我们的研究强调了线粒体动态平衡对睾丸间质细胞类固醇生成功能的重要性。
