ArticleJournal of biomedical science2012
Endoplasmic reticulum stress mediating downregulated StAR and 3-beta-HSD and low plasma testosterone caused by hypoxia is attenuated by CPU86017-RS and nifedipine.
Article in Journal of biomedical science, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers.
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Who cites it
17 citing papers in PubMed, 38 citations in OpenAlex.
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- Obesity impairs spermatogenesis via Leydig cell ferroptosis induced by liver-derived exosomal miR-122-5p.Communications biology · 2026Article
- Novel circNSD2 promotes proliferation and testosterone synthesis while inhibiting apoptosis in bovine Leydig cells.Frontiers in veterinary science · 2026Article
- Omega-3 polyunsaturated fatty acids ameliorate high-fat-diet-induced structural and functional impairments of testicular tissue via ER stress inhibition.Transgenic research · 2025Article
- Review
- Linagliptin and Vitamin D3 Synergistically Rescue Testicular Steroidogenesis and Spermatogenesis in Cisplatin-Exposed Rats: The Crosstalk of Endoplasmic Reticulum Stress with NF-κB/iNOS Activation.Molecules (Basel, Switzerland) · 2022Article
- Proteomic analysis reveals proteins and pathways associated with declined testosterone production in male obese mice after chronic high-altitude exposure.Frontiers in endocrinology · 2022Article
- Obstructive Sleep Apnea Is Associated With Low Testosterone Levels in Severely Obese Men.Frontiers in endocrinology · 2021Observational
- The Role of Endoplasmic Reticulum Stress Response in Male Reproductive Physiology and Pathology: A Review.The world journal of men's health · 2020Review
- Alterations of estrous cycle, 3β hydroxysteroid dehydrogenase activity and progesterone synthesis in female rats after exposure to hypobaric hypoxia.Scientific reports · 2020Article
- LaInternational journal of nanomedicine · 2020Article
- Impact of high altitude on key determinants of female reproductive health: a review.International journal of biometeorology · 2018Review
- Hypoxia reduces testosterone synthesis in mouse Leydig cells by inhibiting NRF1-activated StAR expression.Oncotarget · 2017Article
- Male fertility is reduced by chronic intermittent hypoxia mimicking sleep apnea in mice.Sleep · 2014Article
- Berberine, an epiphany against cancer.Molecules (Basel, Switzerland) · 2014Review
- Hypoxia/oxidative stress alters the pharmacokinetics of CPU86017-RS through mitochondrial dysfunction and NADPH oxidase activation.Acta pharmacologica Sinica · 2013Article
- Depressed calcium-handling proteins due to endoplasmic reticulum stress and apoptosis in the diabetic heart are attenuated by argirein.Naunyn-Schmiedeberg's archives of pharmacology · 2013Article
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Authors and funding
6 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundHypoxia exposure initiates low serum testosterone levels that could be attributed to downregulated androgen biosynthesizing genes such as StAR (steroidogenic acute regulatory protein) and 3-beta-HSD (3-beta-hydroxysteroid dehydrogenase) in the testis. It was hypothesized that these abnormalities in the testis by hypoxia are associated with oxidative stress and an increase in chaperones of endoplasmic reticulum stress (ER stress) and ER stress could be modulated by a reduction in calcium influx. Therefore, we verify that if an application of CPU86017-RS (simplified as RS, a derivative to berberine) could alleviate the ER stress and depressed gene expressions of StAR and 3-beta-HSD, and low plasma testosterone in hypoxic rats, these were compared with those of nifedipine.
methodsAdult male Sprague-Dawley rats were randomly divided into control, hypoxia for 28 days, and hypoxia treated (mg/kg, p.o.) during the last 14 days with nifedipine (Nif, 10) and three doses of RS (20, 40, 80), and normal rats treated with RS isomer (80). Serum testosterone (T) and luteinizing hormone (LH) were measured. The testicular expressions of biomarkers including StAR, 3-beta-HSD, immunoglobulin heavy chain binding protein (Bip), double-strand RNA-activated protein kinase-like ER kinase (PERK) and pro-apoptotic transcription factor C/EBP homologous protein (CHOP) were measured.
resultsIn hypoxic rats, serum testosterone levels decreased and mRNA and protein expressions of the testosterone biosynthesis related genes, StAR and 3-beta-HSD were downregulated. These changes were linked to an increase in oxidants and upregulated ER stress chaperones: Bip, PERK, CHOP and distorted histological structure of the seminiferous tubules in the testis. These abnormalities were attenuated significantly by CPU86017-RS and nifedipine.
conclusionDownregulated StAR and 3-beta-HSD significantly contribute to low testosterone in hypoxic rats and is associated with ER stress which mediates testis damage caused by oxygen deprivation. CPU86017-RS is potential in ameliorating hypoxia-induced testicular injuries, possibly by its calcium antagonist effects on the testis.
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