Age-related increase in mitochondrial superoxide generation in the testosterone-producing cells of Brown Norway rat testes: relationship to reduced steroidogenic function?

Aging in Brown Norway rats is accompanied by the reduced production of testosterone by the Leydig cells, the testicular cells responsible for synthesizing and secreting this essential steroid. As yet, the mechanism by which Leydig cell steroidogenesis is reduced is unknown. Herein we assess the prod...

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Bibliographic Details
Published in:Experimental gerontology 2001-08, Vol.36 (8), p.1361-1373
Main Authors: Chen, Haolin, Cangello, David, Benson, Scott, Folmer, Janet, Zhu, Hong, Trush, Michael A., Zirkin, Barry R.
Format: Article
Language:English
Subjects:
Aging
Aging - metabolism
Animals
Leydig cells
Leydig Cells - metabolism
Leydig Cells - ultrastructure
Lucigenin
Luminescent Measurements
Male
Microscopy, Electron
Mitochondria - metabolism
Mitochondrial superoxide generation
Rat
Rats
Rats, Inbred BN
Reactive Oxygen Species - metabolism
Superoxides - metabolism
Testis
Testosterone - biosynthesis
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Summary:Aging in Brown Norway rats is accompanied by the reduced production of testosterone by the Leydig cells, the testicular cells responsible for synthesizing and secreting this essential steroid. As yet, the mechanism by which Leydig cell steroidogenesis is reduced is unknown. Herein we assess the production of mitochondrial reactive oxygen species by intact Leydig cells isolated from the testes of young and old rats. To this end, Leydig cells were incubated with lucigenin (bis- N-methylacridinium nitrate), a probe that enters cells, localizes to mitochondria, and yields a significant chemiluminescent response following its reaction with intramitochondrial superoxide. Leydig cells from old rats elicited significantly greater lucigenin-derived chemiluminescence (LDCL) than those from young rats. Electron microscopic stereological analysis revealed that the absolute volume of mitochondria in the old cells was reduced from that in the young. These results, taken together, suggest that there are age-related changes in the production of reactive oxygen species by the mitochondria of Leydig cells, with those of old Leydig cells producing significantly greater levels than those of young Leydig cells. The results are consistent with the proposal that mitochondrial-derived reactive oxygen may play a role in the irreversible decline in the ability of old Leydig cells to produce testosterone.
ISSN:0531-5565
1873-6815
DOI:10.1016/S0531-5565(01)00118-8