PARENT SESSION
IMPACT OF NUTRITION AND AGING ON REPRODUCTIVE FUNCTION
Kent
7:30 AM-10:00 AM

(595) LEYDIG CELL AGING: CYCLIC AMP, StAR, AND THE STEROIDOGENIC ENZYMES.

Luo, Lin Di¹, Chen, Haolin¹, Kim, Jong-Min¹, Ghosh, Rebekah¹, Zirkin, Barry¹, ¹ Division of Reproductive Biology, Baltimore, MD

ABSTRACT- Previous studies have shown that the capacity of Leydig cells from aged (21-24 month-old) Brown Norway rats to produce testosterone is reduced compared to young (4 month-old) rats, and that this is correlated with reductions in StAR, PBR, and the levels and activities of each of the steroidogenic enzymes responsible for converting cholesterol to testosterone. We hypothesize that there must be an initiating change that leads to coordinate downstream changes in the steroidogenic machinery, and thus to reduced testosterone. Herein we examine cAMP production, StAR, and P450 side-chain cleavage enzyme (P450scc) in relationship to testosterone production by Leydig cells isolated from Brown Norway rats of 4, 9, 15 and 20 months of age. Significant reductions in testosterone production in response to maximally stimulating LH, dbcAMP or 22-hydroxycholesterol were seen in cells from 15 month-old rats. LH-stimulated intracellular cAMP levels declined significantly by 9 months of age, and then declined further at 15 and 20 months; by age 20 months, cAMP production was reduced by approximately 50% compared to production by young cells. Significant decreases also were seen in StAR and P450scc protein and mRNA by 9 months, as assessed by Western and Northern blot, respectively; StAR protein was reduced by about 30% at that time, and by 80% in cells from 15 month-old rats, while P450scc protein was reduced by about 50% at 15 months. These results indicate that significant changes in each of cAMP, StAR and P450scc precede changes in testosterone production. From these data, we speculate that aging in some way results in reduced intracellular cAMP, and that, as a consequence, there are reductions in cholesterol transport and/or cholesterol metabolism that ultimately result in reduced testosterone production. (Supported by a program project grant from the National Institute on Aging, PO1 AG08321).

KEY WORDS: Leydig Cell, aging, cyclic AMP, StAR