TY - JOUR
T1 - Age induced nitroso-redox imbalance leads to subclinical hypogonadism in Male mice
AU - Lee, John Alden
AU - Kuchakulla, Manish
AU - Arora, Himanshu
AU - Kulandavelu, Shathiyah
AU - Gonzalez, Evert
AU - Masterson, Thomas A.
AU - Hare, Joshua M.
AU - Kaiser, Ursula B.
AU - Ramasamy, Ranjith
N1 - Publisher Copyright:
Copyright © 2019 Lee, Kuchakulla, Arora, Kulandavelu, Gonzalez, Masterson, Hare, Kaiser and Ramasamy. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
Copyright:
Copyright 2019 Elsevier B.V., All rights reserved.
PY - 2019
Y1 - 2019
N2 - Objective: The cause of age-related changes in testosterone remains unclear. We hypothesized that increased nitroso-redox imbalance with aging could affect testosterone production. Materials and Methods: We measured several markers of nitroso-redox imbalance (4-HNE, 3-NT, and NT) 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 young (<2 months), middle-aged (2-6 months), and aged (>12 months) mice. Finally, to elucidate the susceptibility of testes to nitroso-redox imbalance, we measured 4-HNE protein levels in the testes of WT and KO mice. Results: We identified 4-HNE as a reliable marker of nitroso-redox imbalance, as evidenced by increased protein levels in serum of GSNOR KO mice compared with WT mice. We demonstrated that 4-HNE serum protein levels increase in WT mice with age but do not accumulate in the testes. We also found that T levels were similar in all age groups. Interestingly, we found that serum LH levels in aged and middle-aged mice were increased when compared to young mice (n = 5) consistent with the phenotype of subclinical hypogonadism. Conclusions: Increased serum 4-HNE and LH levels without changes in T with age suggest that nitroso-redox imbalance is associated with subclinical hypogonadism in aged mice. Recognizing the relationship and etiology of a currently poorly understood classification of hypogonadism could be a paradigm shift in how age-related testosterone change is diagnosed and treated.
AB - Objective: The cause of age-related changes in testosterone remains unclear. We hypothesized that increased nitroso-redox imbalance with aging could affect testosterone production. Materials and Methods: We measured several markers of nitroso-redox imbalance (4-HNE, 3-NT, and NT) 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 young (<2 months), middle-aged (2-6 months), and aged (>12 months) mice. Finally, to elucidate the susceptibility of testes to nitroso-redox imbalance, we measured 4-HNE protein levels in the testes of WT and KO mice. Results: We identified 4-HNE as a reliable marker of nitroso-redox imbalance, as evidenced by increased protein levels in serum of GSNOR KO mice compared with WT mice. We demonstrated that 4-HNE serum protein levels increase in WT mice with age but do not accumulate in the testes. We also found that T levels were similar in all age groups. Interestingly, we found that serum LH levels in aged and middle-aged mice were increased when compared to young mice (n = 5) consistent with the phenotype of subclinical hypogonadism. Conclusions: Increased serum 4-HNE and LH levels without changes in T with age suggest that nitroso-redox imbalance is associated with subclinical hypogonadism in aged mice. Recognizing the relationship and etiology of a currently poorly understood classification of hypogonadism could be a paradigm shift in how age-related testosterone change is diagnosed and treated.
KW - 4-hydroxynonenal
KW - Aging
KW - Compensated hypogonadism
KW - Nitrosative stress
KW - Nitroso-redox imbalance
KW - S-nitrosoglutathione reductase
KW - Subclinical hypogonadism
UR - http://www.scopus.com/inward/record.url?scp=85066609814&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85066609814&partnerID=8YFLogxK
U2 - 10.3389/fendo.2019.00190
DO - 10.3389/fendo.2019.00190
M3 - Article
AN - SCOPUS:85066609814
VL - 10
JO - Frontiers in Endocrinology
JF - Frontiers in Endocrinology
SN - 1664-2392
IS - MAR
M1 - 190
ER -