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 whi ch this occurs is unknown. Based on the observations that reactive oxygen i s capable of damaging components of the steroidogenic pathway and that reac tive oxygen is produced during steroidogenesis itself, we hypothesized that long-term suppression of steroidogenesis might inhibit or prevent age-rela ted deficits in Leydig cell testosterone production. To test this, we admin istered contraceptive doses of testosterone to groups of young (3 months ol d) 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 th e previously suppressed Leydig cells to produce testosterone. Two months af ter removing the implants, when the rats of the two groups were 13 and 23 m onths of age, respectively, the Leydig cells in both cases were found to pr oduce testosterone at the high levels of young Leydig cells, whereas signif icantly lower levels were produced by the 23-month-old controls. Thus, by p lacing the Leydig cells in a state of steroidogenic "hibernation," the redu ctions in Leydig cell testosterone production that invariably accompany agi ng did not occur. If hormonal contraception in the human functions the same way, the adverse consequences of reduced testosterone in later life (osteo porosis, reduced muscle mass, reduced libido, mood swings, etc.) might be d elayed or prevented.