ArticleBiology of reproduction2021
Sirt1 and Nrf2: regulation of Leydig cell oxidant/antioxidant intracellular environment and steroid formation†.
Article in Biology of reproduction, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 28 papers, 1 of them a synthesis that pooled it.
What it found
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Who cites it
28 citing papers in PubMed, 1 synthesis or guideline pooled it, 54 citations in OpenAlex.
- Protective effects of exogenous melatonin therapy against oxidative stress to male reproductive tissue caused by anti-cancer chemical and radiation therapy: a systematic review and meta-analysis of animal studies.Frontiers in endocrinology · 2023Pooled it
- Male testosterone synthesis disorders: oxidative stress pathways, regulatory mechanisms, potential of antioxidant therapy, and botanical medicine prospects.Asian journal of andrology · 2026Review
- Natural Small Molecules Targeting Oxidative Stress and Redox Homeostasis in Aging: Mechanisms and Therapeutic Potential.Antioxidants (Basel, Switzerland) · 2026Review
- Review
- Lifestyle implications of the paradox and management of oxidative stress in sperm.The Journal of physiology · 2026Review
- Modulation of Oxidative Stress, Inflammation, and Apoptosis and Restoration of Sirt1/Nrf2/HO-1 Signaling by Diosmin Protect Against Diabetes-Induced Testicular Damage in Rats.International journal of molecular sciences · 2026Article
- Oxidative Stress andInternational journal of molecular sciences · 2026Review
- Effects of Aging on Mammalian Spermatogenesis From a Cellular Perspective.Molecular reproduction and development · 2025Review
- Review
- The REDOX balance in the prefrontal cortex is positively modulated by aerobic exercise and altered by overfeeding.Scientific reports · 2025Article
- Gentiopicroside Alleviates Atherosclerosis by Suppressing Reactive Oxygen Species-Dependent NLRP3 Inflammasome Activation in Vascular Endothelial Cells via SIRT1/Nrf2 Pathway.Chinese journal of integrative medicine · 2025Article
- Do Lifestyle Interventions Mitigate the Oxidative Damage and Inflammation Induced by Obesity in the Testis?Antioxidants (Basel, Switzerland) · 2025Review
- The effects of the Wnt/β-catenin signaling pathway on the in vitro differentiation of rat BMSCs into leydig cells.Scientific reports · 2025Article
- The critical role of Sirt1 in ischemic stroke.Frontiers in pharmacology · 2025Review
- Functional Food Nutrients, Redox Resilience Signaling and Neurosteroids for Brain Health.International journal of molecular sciences · 2024Review
- Positive association between serum bilirubin within the physiological range and serum testosterone levels.BMC endocrine disorders · 2024Article
- Reproductive Ageing: Current insights and a potential role of NAD in the reproductive health of aging fathers and their children.Reproduction (Cambridge, England) · 2024Review
- Phosphatidylserine Counteracts the High Stocking Density-Induced Stress Response, Redox Imbalance and Immunosuppression in FishAntioxidants (Basel, Switzerland) · 2024Article
- Bioactive Compounds Protect Mammalian Reproductive Cells from Xenobiotics and Heat Stress-Induced Oxidative Distress via Nrf2 Signaling Activation: A Narrative Review.Antioxidants (Basel, Switzerland) · 2024Review
- Anthocyanins fromPharmaceuticals (Basel, Switzerland) · 2024Article
Corrections and comments
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Authors and funding
3 authors at 2 institutions in 2 countries.
Funding
Abstract
Previous studies reported that, with aging, Leydig cell intracellular antioxidants are reduced in concentration and intracellular ROS levels increase, suggesting that oxidant/antioxidant imbalance may contribute to the reduced testosterone production that characterizes the aging cells. As yet, little is known about how the Leydig cell oxidant/antioxidant environment is regulated. Sirt1, an enzyme that deacetylates transcription factors, and the transcription factor Nrf2, have been shown to be associated with cellular response to oxidative stress. We hypothesized that Sirt1 and/or Nrf2 might be involved in regulating the oxidant/antioxidant environment of Leydig cells, and therefore, the testosterone production. We found that Sirt1 and Nrf2 are present in the Leydig cells of Brown Norway rats, though reduced in aged cells. In MA-10 cells in which Sirt1 or Nrf2 were suppressed by nicotinamide (NAM) or ML385, respectively, or in which siRNAs were used for knockdown of Sirt1 or Nrf2, increased ROS levels and decreased progesterone production occurred. In rat Leydig cells, inhibition of Sirt1 by culturing the cells with NAM resulted in increased ROS and reduced testosterone production, and subsequent removal of NAM from the culture medium resulted in increased testosterone production. Activation of rat Leydig cells Sirt1 with honokiol or of Nrf2 with sulforaphane resulted in the maintenance of testosterone production despite the exposure of the cells to oxidizing agent. These results, taken together, suggest that Sirt1 and Nrf2 are involved in maintaining the Leydig cell oxidant/antioxidant environment, and thus in maintaining steroid production.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.