Regulation of Leydig cell steroidogenic function during aging

This article summarizes a talk on Leydig cell aging presented at the 1999 A nnual Meeting of the Society for the Study of Reproduction. In the Brown No rway rat, serum testosterone levels decrease with aging, accompanied by inc reases in serum FSH. The capacity of Leydig cells to produce testosterone i s higher in young than in old rats. Binding studies with hCG revealed reduc ed receptor number in old vs. young Leydig cells. In response to incubation with LH, cAMP production was found to be reduced in old vs. young Leydig c ells, indicating that signal tranduction mechanisms in the old cells are af fected by aging. Steroidogenic acute regulatory protein and mRNA levels are reduced in old Leydig cells, suggesting that there may be deficits in the transport of cholesterol to the inner mitochondrial membrane of aged cells. The activity of P450 side-chain cleavage enzyme is reduced in old vs, youn g cells, as are the activities of each of 3 beta-hydroxysteroid dehydrogena se, 17 alpha-hydroxylase/C17-20 lyase, and 17-ketosteroid reductase. Serum LH levels do not differ between young and old rats, and the administration of LH failed to induce old Leydig cells to produce high (young) testosteron e levels, suggesting that the cause of age-related reductions in steroidoge nesis is not LH deficits. We hypothesized that reactive oxygen, produced as a by-product of steroidogenesis itself, might be responsible for age-relat ed reductions in testosterone production by the Leydig cells. Consistent wi th this, long-term suppression of steroidogenesis was found to prevent or d elay the reduced steroidogenesis that accompanies Leydig cell aging. A poss ible explanation of this finding is that longterm suppression of steroidoge nesis prevents free radical damage to the cells by suppressing the producti on of the reactive oxygen species that are a by-product of steroidogenesis itself.