An analysis of the age-related decline in testicular steroidogenesis in the rat.

The effect of aging in rats on serum and intratesticular testosterone levels, microsomal steroidogenic enzyme activities and microsomal cytochrome P-450 was studied. Serum testosterone levels were highest in 11-wk-old rats, declined at age 16 wk and further declined between ages 7 and 21 mo. Intratesticular testosterone levels in 21-mo-old rats were significantly lower than those of the other groups. The activity of 17 alpha-hydroxylase and C17-20 lyase, as well as cytochrome P-450, decreased significantly in 21-mo-old rats. The activity of 17 beta-hydroxysteroid oxidoreductase increased from 11 wk to 16 wk of age and then declined by 21 mo of age to the levels of 11-wk-old animals. Similar changes in delta 5-3,3-hydroxysteroid dehydrogenase coupled with delta 5-delta 4 isomerase activities were observed, but were not statistically significant. These results suggest that the decline in testosterone production in old rats is predominantly a result of decreased oxygenase activity. Inasmuch as oxygenases are gonadotropin dependent, our results support the hypothesis that gonadotropin deficiency is the major factor responsible for Leydig cell dysfunction in old rats. Further, the decline in the ratio of 17 alpha-hydroxylase to C17-20 lyase with aging suggests that other factors affect these enzymes as well as the reduction in cytochrome P-450.