4-Methylcatechol inhibits cell growth and testosterone production in TM3 Leydig cells by reducing mitochondrial activity

Li, C.-J.; Jiang, Yanwen; Chen, S.-X.; Li, H.-J.; Chen, L.; Liu, Y.-T.; Gao, Shan; Zhao, Yun; Zhu, Xiaoyan; Wang, H.-T.; Wang, F.-G.; Zheng, Lianwen; Zhou, Xu

doi:10.1111/and.12581

Cited by 7 publications

(3 citation statements)

References 21 publications

(18 reference statements)

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“…Several earlier studies applied MA-10 [ 39 , 40 , 41 , 42 , 43 , 44 , 45 , 46 , 47 ], BLTK1 [ 20 , 35 ], or TM3 cells [ 48 , 49 , 50 , 51 ] to analyze effects of endogenous and exogenous substances on steroidogenesis by measuring T production using antibody-based methods. In most of these studies there is only limited information available on the specificity of the antibody used, and the commercial suppliers mostly included only a limited number of steroid metabolites in their characterization.…”

Section: Discussionmentioning

confidence: 99%

Currently available murine Leydig cell lines can be applied to study early steps of steroidogenesis but not testosterone synthesis

Engeli

Fürstenberger

Kratschmar

et al. 2018

Heliyon

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Androgen biosynthesis in males occurs to a large extent in testicular Leydig cells. This study focused on the evaluation of three murine Leydig cell lines as potential screening tool to test xenobiotics interfering with gonadal androgen synthesis. The final step of testosterone (T) production in Leydig cells is catalyzed by the enzyme 17β-hydroxysteroid dehydrogenase 3 (17β-hsd3). The endogenous 17β-hsd3 mRNA expression and Δ4-androstene-3,17-dione (AD) to T conversion were determined in the murine cell lines MA-10, BLTK1 and TM3. Additionally, effects of 8-Br-cAMP and forskolin stimulation on steroidogenesis and T production were analyzed. Steroids were quantified in supernatants of cells using liquid chromatography–tandem mass spectrometry. Unstimulated cells incubated with AD produced only very low T but substantial amounts of the inactive androsterone. Stimulated cells produced low amounts of T, moderate amounts of AD, but high amounts of progesterone. Gene expression analyses revealed barely detectable 17β-hsd3 levels, absence of 17β-hsd5 (Akr1c6), but substantial 17β-hsd1 expression in all three cell lines. Thus, MA-10, BLTK1 and TM3 cells are not suitable to study the expression and activity of the gonadal T synthesizing enzyme 17β-hsd3. The low T production reported in stimulated MA-10 cells are likely a result of the expression of 17β-hsd1. This study substantiates that the investigated Leydig cell lines MA-10, BLTK1, and TM3 are not suitable to study gonadal androgen biosynthesis due to altered steroidogenic pathways. Furthermore, this study emphasizes the necessity of mass spectrometry-based steroid quantification in experiments using steroidogenic cells such as Leydig cells.

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Section: Discussionmentioning

confidence: 99%

Currently available murine Leydig cell lines can be applied to study early steps of steroidogenesis but not testosterone synthesis

Engeli

Fürstenberger

Kratschmar

et al. 2018

Heliyon

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“…Mitochondria are very important for Leydig cell survival and testosterone production ( Kong et al, 2017a ). Previous studies have revealed that mitochondrial dysfunction of Leydig cells significantly reduced testosterone production and serum testosterone ( Li et al, 2017a ; Kong et al, 2017b ; Goncalves et al, 2018 ). Here, we found that triptolide activated the mitochondrial apoptosis pathway, increased cell ROS, and depolarized mitochondrial membrane potential.…”

Section: Discussionmentioning

confidence: 99%

Triptolide Induces Leydig Cell Apoptosis by Disrupting Mitochondrial Dynamics in Rats

Chang

et al. 2021

Front. Pharmacol.

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Triptolide is widely used in the clinical treatment of various diseases. Side effects, including reproductive toxicity to male patients, limit its application. However, no detailed mechanisms or potential intervention targets have been reported. In this study, we show that triptolide activated the mitochondrial apoptosis pathway in rat testicular Leydig cells and induced apoptosis both in vivo and in vitro, which may cause hypoleydigism and impair spermatogenesis. Mechanistically, triptolide-induced dynamin-related protein 1 (Drp1) overexpression, which interfered with mitochondrial dynamic stability to activate the mitochondrial apoptosis pathway. Mdivi-1, a selective Drp1 inhibitor, partially reversed the mitochondrial dynamic disturbance and rat testicular Leydig cell apoptosis induced by triptolide. Inhibiting Drp1 over-activation may be a new strategy for mitigating the reproductive toxicity of triptolide.

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“…In addition, recent studies reported that NGF and TrkA can stimulate sperm motility and induce sperm cell acrosome reactions. Furthermore, NGF plays an important role promoting testosterone production, proliferation and differentiation of Leydig cells [ 55 , 56 ]. Similar findings were also reported in human, monkey and rabbit.…”

Section: Discussionmentioning

confidence: 99%

Expression of Nerve Growth Factor and Its Receptor TrkA in the Reproductive System of Adult Zebrafish

Cacialli

2022

Veterinary Sciences

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Nerve growth factor (NGF), a member of the neurotrophin family, has emerged as an active mediator in different crucial events in the peripheral and central nervous system. At the same time, several studies showed that this neurotrophin can also play a role in non-neuronal tissues (e.g., among gonads). In spite of a large number of studies present in mammals, investigations devoted to NGF and its receptor TrkA in the reproductive system of other animal models, such as teleost fish, are scarce. To increase our knowledge of NGF and its receptor in a vertebrate gonads model, the present report describes the expression patterns of ngf and trka mRNA in the testis and ovary of adult zebrafish. By using chromogenic and fluorescence in situ hybridization, we demonstrate that in the testis of adult zebrafish, ngf and its receptor trka are mainly expressed in spermatogony B and spermatocytes. In the ovary of this fish, ngf and trka are expressed at different stages of oocyte development. Altogether, these results show that this neurotrophin and its receptor have an important role in the reproductive system that is conserved during vertebrate evolution.

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4-Methylcatechol inhibits cell growth and testosterone production in TM3 Leydig cells by reducing mitochondrial activity

Cited by 7 publications

References 21 publications

Currently available murine Leydig cell lines can be applied to study early steps of steroidogenesis but not testosterone synthesis

Currently available murine Leydig cell lines can be applied to study early steps of steroidogenesis but not testosterone synthesis

Triptolide Induces Leydig Cell Apoptosis by Disrupting Mitochondrial Dynamics in Rats

Expression of Nerve Growth Factor and Its Receptor TrkA in the Reproductive System of Adult Zebrafish

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