title: Knockout of the transcription factor Nrf2: Effects on testosterone production by aging mouse Leydig cells.
abstract: Aging in rodents and men is associated with reduced serum levels of testosterone and Leydig cell testosterone productions. To further investigate the mechanism by which Leydig cell testosterone production declines, the effect of knocking out Nrf2, a master regulator of phase 2 antioxidant genes, was examined. In wild-type mice, testosterone production and serum testosterone levels remained unchanged through middle age (8 months), but then were reduced significantly by old age (21-24 months). In contrast, serum testosterone levels and Leydig cell testosterone production were reduced significantly in the Nrf2-/- mice as early as middle age, and were reduced further in the aged mice. Reduced steroidogenesis in the knockout mice was associated with reduced antioxidant capacity, and increased expression of protein nitrotyrosine residues, a marker of ROS. These results support the hypothesis that, over time, increases in oxidative stress contribute to or cause the reduced testosterone production that characterizes Leydig cell aging.
authors.affiliation: Department of Biochemistry and Molecular Biology, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD 21205; The Second Affiliated Hospital, Wenzhou Medical University, Wenzhou, Zhejiang, China. Electronic address: hchen13@jhu.edu.
authors.forename: Haolin
authors.initials: H
authors.lastname: Chen
authors.affiliation: Department of Biochemistry and Molecular Biology, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD 21205.
authors.forename: Shiying
authors.initials: S
authors.lastname: Jin
authors.affiliation: The Second Affiliated Hospital, Wenzhou Medical University, Wenzhou, Zhejiang, China.
authors.forename: Jingjing
authors.initials: J
authors.lastname: Guo
authors.affiliation: Department of Environmental Health Sciences, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD 21205.
authors.forename: Ponvijay
authors.initials: P
authors.lastname: Kombairaju
authors.affiliation: Department of Environmental Health Sciences, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD 21205.
authors.forename: Shyam
authors.initials: S
authors.lastname: Biswal
authors.affiliation: Department of Biochemistry and Molecular Biology, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD 21205.
authors.forename: Barry R
authors.initials: BR
authors.lastname: Zirkin
mesh_terms: D000375:Aging / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D002478:Cells, Cultured; D006801:Humans; D007985:Leydig Cells / Q000378:metabolism / Q000502:physiology*; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D051267:NF-E2-Related Factor 2 / Q000235:genetics* / Q000378:metabolism*; D018384:Oxidative Stress; D013739:Testosterone / Q000097:blood / Q000378:metabolism*; D014443:Tyrosine / Q000031:analogs & derivatives / Q000378:metabolism
chemical_list: D051267:NF-E2-Related Factor 2; C495636:Nfe2l2 protein, mouse; C002744:3-nitrotyrosine; D013739:Testosterone; D014443:Tyrosine
keywords: Aging; Leydig cells; Nrf2; Oxidative stress
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