PARENT SESSION
MINISYMPOSIUM XV. Regulation of Steroidogenesis in the Leydig Cell.
11:00 AM-12:30 PM
Harborside E
Chair: Zirkin, Barry¹, ¹

(M46) REGULATION OF LEYDIG CELL AGING.

Zirkin, Barry¹, ¹ Division of Reproductive Biology, Baltimore, Maryland, USA

ABSTRACT- In male Brown Norway rats, as in men, aging is associated with reduced serum testosterone concentration. In the rat, this results from the reduced production of testosterone by the Leydig cells, not from loss of Leydig cells. Average serum LH concentration in Brown Norway rats does not change with age. The administration of LH to old rats failed to restore testosterone production by old Leydig cells to the significantly higher levels produced by young cells. Exposure of old Leydig cells to LH in vitro failed to increase the ability of these cells to produce testosterone. Taken together, these results indicate that old Leydig cells are relatively unresponsive to LH. In comparison to Leydig cells from untreated young rats, Leydig cells from old rats and from young LH-suppressed rats have reduced numbers of LH binding sites. However, both the young LH-suppressed cells and young control cells produce cAMP at high levels compared to the old cells. This suggests that LH receptor number does not explain the relative inability of the old cells to produce cAMP in response to LH. Culture of old cells with dbcAMP for 3 days restored the ability of the cells to produce testosterone at high levels. Incubation of old cells with forskolin resulted in these cells producing the same amount of cAMP as young control cells, suggesting that adenylate cyclase is maintained the in old cells. Taken together, the results suggest that the problem in the signal trasduction pathway of old cells resides in the receptor and G protein coupling. How might aging result in changes in the membrane of old Leydig cells that would result in ineffecient signal transduction? There is extensive evidence that free radical damage contributes to cell aging. In steroidogenic cells, reactive oxygen is produced by the electron transport chain and by the P450 reactions of steroidogenesis. Old Leydig cells produce greater amounts of free radicals than young cells, and have diminished superoxide dismutase. Long-term suppression of sterodogenesis with testosterone implants resulted in suppression of Leydig cell aging. The possibility that free radical damage to LH receptors or G proteins might result in the reduced ability of LH to stimulate cAMP production is under study in our laboratory. (Supported by NIH grant AG08321)

KEY WORDS: aging, Leydig cell, steroidogenesis, cAMP