Long-term suppression of Leydig cell steroidogenesis prevents Leydig cell aging.
Male aging is accompanied by reduced testosterone production by the Leydig cells, the testosterone-producing cells of the testis. The mechanism by which this occurs is unknown. Based on the observations that reactive oxygen is capable of damaging components of the steroidogenic pathway and that reactive oxygen is produced during steroidogenesis itself, we hypothesized that long-term suppression of steroidogenesis might inhibit or prevent age-related deficits in Leydig cell testosterone production. To test this, we administered contraceptive doses of testosterone to groups of young (3 months old) and middle-aged (13 months old) Brown Norway rats via Silastic implants to suppress endogenous Leydig cell testosterone production. After 8 months, the implants were removed, which rapidly (days) restores the ability of the previously suppressed Leydig cells to produce testosterone. Two months after removing the implants, when the rats of the two groups were 13 and 23 months of age, respectively, the Leydig cells in both cases were found to produce testosterone at the high levels of young Leydig cells, whereas significantly lower levels were produced by the 23-month-old controls. Thus, by placing the Leydig cells in a state of steroidogenic "hibernation," the reductions in Leydig cell testosterone production that invariably accompany aging did not occur. If hormonal contraception in the human functions the same way, the adverse consequences of reduced testosterone in later life (osteoporosis, reduced muscle mass, reduced libido, mood swings, etc. ) might be delayed or prevented.
Chen
H
H
Division of Reproductive Biology, Department of Biochemistry, Johns Hopkins University, School of Hygiene and Public Health, 615 North Wolfe Street, Baltimore, MD 21205, USA.
Zirkin
B R
BR
D015067:17-Hydroxysteroid Dehydrogenases / Q000032:analysis; D000375:Aging / Q000502:physiology*; D000818:Animals; D002469:Cell Separation; D016922:Cellular Senescence / Q000502:physiology*; D002786:Cholesterol Side-Chain Cleavage Enzyme / Q000032:analysis; D003577:Cytochrome P-450 Enzyme System / Q000032:analysis; D006913:Hydroxysteroid Dehydrogenases / Q000032:analysis; D007985:Leydig Cells / Q000502:physiology*; D008297:Male; D051381:Rats; D013254:Steroid 17-alpha-Hydroxylase / Q000032:analysis; D013256:Steroids / Q000096:biosynthesis*; D013739:Testosterone / Q000096:biosynthesis / Q000494:pharmacology*
D013256:Steroids; D013739:Testosterone; D003577:Cytochrome P-450 Enzyme System; D015067:17-Hydroxysteroid Dehydrogenases; D006913:Hydroxysteroid Dehydrogenases; D013254:Steroid 17-alpha-Hydroxylase; C022433:pregnenolone 17-alpha-hydroxylase; D002786:Cholesterol Side-Chain Cleavage Enzyme