TY - JOUR
T1 - Aging and caloric restriction
T2 - Effects on Leydig cell steroidogenesis
AU - Chen, Haolin
AU - Luo, Lin-Di
AU - Liu, June
AU - Brown, Terry Ray
AU - Zirkin, Barry R.
N1 - Funding Information:
Supported by grants from the National Institute on Aging (AG21092 to BZ and AG20999 to TB).
PY - 2005/6
Y1 - 2005/6
N2 - We have shown previously that testosterone concentration in the blood serum of Brown Norway rat becomes reduced with aging, and that this results from reduced testosterone production by individual Leydig cells. Herein we examine the effects of caloric restriction (CR), an intervention shown to delay or inhibit age-associated pathologic and biologic changes in a number of systems and organisms, on Leydig cell steroidogenic function. CR (40%) was initiated in 4 month-old Brown Norway rats, and continued through age 34 months. Serum testosterone concentration in the ad libitum (AL)-fed controls was reduced by 30% from 5 to 13 months, by another 67% through 25 months, and then was sustained through 34 months. For the CR rats, the serum testosterone level was reduced to 45% of AL controls by 5 months, only 6 weeks after the initiation of the CR regimen. There was no further reduction through 25 months, at which time serum testosterone concentration in CR animals was significantly higher than in AL controls. By age 28-34 months, there was no significant difference between the two diets. The weights of prostate and seminal vesicle, two biomarkers of serum androgen levels, were consistent with the changes in serum testosterone concentration in both AL and CR animals. The ability of isolated Leydig cells to produce testosterone in vitro also paralleled the age- and CR-related changes in serum testosterone concentration. CR resulted in a rapid, 36% reduction in testosterone production from control by age 5 months. In contrast to cells from the AL rats, there were no further decreases in testosterone production through age 25 months. Indeed, Leydig cells from the 25 month-old CR rats produced significantly greater amounts of testosterone than cells from the 25 month-old AL rats. These results indicate that short-term CR results in the suppression of Leydig cell function and in reduction in serum testosterone levels. The significantly higher concentrations of serum testosterone concentration, and increased Leydig cell testosterone production, elicited by CR in 25 month-old rats compared to AL controls suggest that long-term CR can transiently suppress the reductions in steroidogenesis that are characteristic of aging.
AB - We have shown previously that testosterone concentration in the blood serum of Brown Norway rat becomes reduced with aging, and that this results from reduced testosterone production by individual Leydig cells. Herein we examine the effects of caloric restriction (CR), an intervention shown to delay or inhibit age-associated pathologic and biologic changes in a number of systems and organisms, on Leydig cell steroidogenic function. CR (40%) was initiated in 4 month-old Brown Norway rats, and continued through age 34 months. Serum testosterone concentration in the ad libitum (AL)-fed controls was reduced by 30% from 5 to 13 months, by another 67% through 25 months, and then was sustained through 34 months. For the CR rats, the serum testosterone level was reduced to 45% of AL controls by 5 months, only 6 weeks after the initiation of the CR regimen. There was no further reduction through 25 months, at which time serum testosterone concentration in CR animals was significantly higher than in AL controls. By age 28-34 months, there was no significant difference between the two diets. The weights of prostate and seminal vesicle, two biomarkers of serum androgen levels, were consistent with the changes in serum testosterone concentration in both AL and CR animals. The ability of isolated Leydig cells to produce testosterone in vitro also paralleled the age- and CR-related changes in serum testosterone concentration. CR resulted in a rapid, 36% reduction in testosterone production from control by age 5 months. In contrast to cells from the AL rats, there were no further decreases in testosterone production through age 25 months. Indeed, Leydig cells from the 25 month-old CR rats produced significantly greater amounts of testosterone than cells from the 25 month-old AL rats. These results indicate that short-term CR results in the suppression of Leydig cell function and in reduction in serum testosterone levels. The significantly higher concentrations of serum testosterone concentration, and increased Leydig cell testosterone production, elicited by CR in 25 month-old rats compared to AL controls suggest that long-term CR can transiently suppress the reductions in steroidogenesis that are characteristic of aging.
KW - Aging
KW - Brown Norway rat
KW - Caloric restriction
KW - Leydig cell
KW - Testosterone
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U2 - 10.1016/j.exger.2005.03.011
DO - 10.1016/j.exger.2005.03.011
M3 - Article
C2 - 15935587
AN - SCOPUS:21244488519
SN - 0531-5565
VL - 40
SP - 498
EP - 505
JO - Experimental Gerontology
JF - Experimental Gerontology
IS - 6
ER -