Abstract
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.
| Original language | English (US) |
|---|---|
| Article number | 190 |
| Journal | Frontiers in Endocrinology |
| Volume | 10 |
| Issue number | MAR |
| DOIs | |
| State | Published - Jan 1 2019 |
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Keywords
- 4-hydroxynonenal
- Aging
- Compensated hypogonadism
- Nitrosative stress
- Nitroso-redox imbalance
- S-nitrosoglutathione reductase
- Subclinical hypogonadism
ASJC Scopus subject areas
- Endocrinology, Diabetes and Metabolism
Cite this
Age induced nitroso-redox imbalance leads to subclinical hypogonadism in Male mice. / Lee, John Alden; Kuchakulla, Manish; Arora, Himanshu; Kulandavelu, Shathiyah; Gonzalez, Evert; Masterson, Thomas A.; Hare, Joshua M.; Kaiser, Ursula B.; Ramasamy, Ranjith.
In: Frontiers in Endocrinology, Vol. 10, No. MAR, 190, 01.01.2019.Research output: Contribution to journal › Article
}
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
PY - 2019/1/1
Y1 - 2019/1/1
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 -