MP59-15 AGE INDUCED NITROSO-REDOX IMBALANCE IS ASSOCIATED WITH SUBCLINICAL HYPOGONADISM (2019)

You have accessJournal of UrologySexual Function/Dysfunction: Basic Research & Pathophysiology (MP59)1 Apr 2019MP59-15 AGE INDUCED NITROSO-REDOX IMBALANCE IS ASSOCIATED WITH SUBCLINICAL HYPOGONADISM John Lee*, Manish Kuchakulla, Himanshu Arora, Shathiyah Kulandavelu, Evert Gonzalez, Thomas Masterson, Joshua Hare, and Ranjith Ramasamy John Lee*John Lee* More articles by this author , Manish KuchakullaManish Kuchakulla More articles by this author , Himanshu AroraHimanshu Arora More articles by this author , Shathiyah KulandaveluShathiyah Kulandavelu More articles by this author , Evert GonzalezEvert Gonzalez More articles by this author , Thomas MastersonThomas Masterson More articles by this author , Joshua HareJoshua Hare More articles by this author , and Ranjith RamasamyRanjith Ramasamy More articles by this author View All Author Informationhttps://doi.org/10.1097/01.JU.0000556727.56027.9cAboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVES: The cause for age-related changes in testosterone remains unclear. We hypothesized that increased nitroso-redox imbalance with aging could affect testosterone production. METHODS: Using western blotting we assessed several markers of nitroso-redox imbalance (4-HNE, NT, 3-NT, and S-NO) in serum of S-nitrosoglutathione reductase knock out (GSNOR KO) mice that have increased nitroso-redox imbalance and compared these to wild type (WT) mice. We evaluated the impact of age-induced nitroso-redox imbalance on serum luteinizing hormone (LH) and testosterone (T) in WT mice at pre-pubertal (< 2months), middle-aged (2-6 months), and aged (>12 months) mice. Finally, we evaluated whether ascorbate, an antioxidant, can be used to reverse age-induced nitroso-redox imbalance. RESULTS: We identified 4-HNE as a reliable marker of nitroso-redox imbalance as evidenced by increased expression in serum of GSNOR KO mice compared with WT mice. We demonstrated that 4-HNE expression in serum increases in WT mice with aging (Figure 1). We also identified that testosterone levels were similar in middle-aged and aged mice and as expected, were increased compared to pre-pubertal mice. Interestingly, we found that serum LH levels in aged (n=8) and middle-aged (n=5) mice were increased when compared to pre-pubertal mice (n=5) consistent with the phenotype of subclinical hypogonadism (Figure 2). GSNOR KO mice treated with ascorbate for 5 weeks had reduced the expression of 4-HNE and increased serum T levels compared to untreated mice. CONCLUSIONS: Increasing 4-HNE expression with age suggests that nitroso-redox imbalance is a possible mechanism for subclinical hypogonadism. Recognizing the relationship and etiology on a currently poorly understood classification of hypogonadism could be a paradigm shift in how age-related testosterone change is diagnosed and treated. Source of Funding: None Miami, FL© 2019 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 201Issue Supplement 4April 2019Page: e866-e866 Advertisement Copyright & Permissions© 2019 by American Urological Association Education and Research, Inc.MetricsAuthor Information John Lee* More articles by this author Manish Kuchakulla More articles by this author Himanshu Arora More articles by this author Shathiyah Kulandavelu More articles by this author Evert Gonzalez More articles by this author Thomas Masterson More articles by this author Joshua Hare More articles by this author Ranjith Ramasamy More articles by this author Expand All Advertisement PDF downloadLoading ...