Medar Marija L J, Marinkovic Dijana Z, Kojic Zvezdana, Becin Alisa P, Starovlah Isidora M, Kravic-Stevovic Tamara, Andric Silvana A, Kostic Tatjana S
Department of Biology and Ecology, Faculty of Sciences, University of Novi Sad, 21102 Novi Sad, Serbia.
Institute of Physiology, Faculty of Medicine, University of Belgrade, 11000 Belgrade, Serbia.
Life (Basel). 2020 Dec 31;11(1):19. doi: 10.3390/life11010019.
Knowledge about the relationship between steroidogenesis and the regulation of the mitochondrial bioenergetics and dynamics, in steroidogenic cells, is not completely elucidated. Here we employed in vivo and ex vivo experimental models to analyze mitochondrial physiology in Leydig cells depending on the different LH-cAMP environments. Activation of LH-receptor in rat Leydig cells ex and in vivo triggered cAMP, increased oxygen consumption, mitoenergetic and steroidogenic activities. Increased mitoenergetic activity i.e., ATP production is achieved through augmented glycolytic ATP production and a small part of oxidative phosphorylation (OXPHOS). Transcription of major genes responsible for mitochondrial dynamics was upregulated for (regulator of mitogenesis and function) and downregulated for (main fission marker), , and (mitophagy markers). Leydig cells from gonadotropin-treated rats show increased mitogenesis confirmed by increased mitochondrial mass, increased mtDNA, more frequent mitochondria observed by a transmission electron microscope and increased expression of subunits of respiratory proteins /CYTC and COX4. Opposite, Leydig cells from hypogonadotropic-hypogonadal rats characterized by low LH-cAMP, testosterone, and ATP production, reduced markers of mitogenesis and mitofusion (, ) associated with reduced mtDNA content. Altogether results underline LH-cAMP signaling as an important regulator of mitochondrial physiology arranging mitochondrial dynamics, bioenergetic and steroidogenic function in Leydig cells.
关于类固醇生成与类固醇生成细胞中线粒体生物能量学和动力学调节之间的关系，目前尚未完全阐明。在这里，我们采用体内和体外实验模型，根据不同的促黄体生成素-环磷酸腺苷（LH-cAMP）环境来分析睾丸间质细胞中的线粒体生理学。大鼠睾丸间质细胞在体内外激活LH受体后会触发cAMP，增加氧气消耗、线粒体能量代谢和类固醇生成活性。线粒体能量代谢活性增加，即ATP产生，是通过增加糖酵解ATP产生以及一小部分氧化磷酸化（OXPHOS）来实现的。负责线粒体动力学的主要基因转录，对于（有丝分裂和功能的调节因子）上调，而对于（主要分裂标记）、、和（线粒体自噬标记）下调。促性腺激素处理大鼠的睾丸间质细胞显示有丝分裂增加，这通过线粒体质量增加、线粒体DNA增加、透射电子显微镜观察到的更频繁的线粒体以及呼吸蛋白/CYTC和COX4亚基的表达增加得以证实。相反，促性腺激素功能减退-性腺功能减退大鼠的睾丸间质细胞，其特征是LH-cAMP、睾酮和ATP产生水平低，有丝分裂和线粒体融合标记物（、）减少，与线粒体DNA含量降低有关。总之，这些结果强调了LH-cAMP信号作为线粒体生理学的重要调节因子，在睾丸间质细胞中安排线粒体动力学、生物能量学和类固醇生成功能。
