Chen Haolin, Luo Lindi, Liu June, Brown Terry, Zirkin Barry R
Division of Reproductive Biology, Department of Biochemistry and Molecular Biology, Johns Hopkins University, Bloomberg School of Public Health, 615 North Wolfe Street, Baltimore, MD 21205, USA.
Exp Gerontol. 2005 Jun;40(6):498-505. doi: 10.1016/j.exger.2005.03.011.
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.
我们之前已经表明，雄性挪威棕色大鼠血清中的睾酮浓度会随着衰老而降低，这是由于单个睾丸间质细胞产生的睾酮减少所致。在此，我们研究热量限制（CR）对睾丸间质细胞类固醇生成功能的影响，热量限制是一种已被证明能延缓或抑制许多系统和生物体中与年龄相关的病理和生物学变化的干预措施。对4月龄的雄性挪威棕色大鼠开始进行40%的热量限制，并持续到34月龄。随意进食（AL）的对照组血清睾酮浓度在5至13月龄时降低了30%，到25月龄时又降低了67%，然后在34月龄时保持稳定。对于热量限制组的大鼠，在开始热量限制方案仅6周后的5月龄时，血清睾酮水平降至AL对照组的45%。在25月龄之前没有进一步降低，此时热量限制组动物的血清睾酮浓度显著高于AL对照组。到28 - 34月龄时，两种饮食组之间没有显著差异。前列腺和精囊的重量是血清雄激素水平的两个生物标志物，在AL组和热量限制组动物中均与血清睾酮浓度的变化一致。体外分离的睾丸间质细胞产生睾酮的能力也与血清睾酮浓度的年龄和热量限制相关变化平行。热量限制导致到5月龄时睾酮生成量从对照水平迅速降低36%。与AL组大鼠的细胞不同，到25月龄时睾酮生成量没有进一步下降。事实上，25月龄热量限制组大鼠的睾丸间质细胞产生的睾酮量明显多于25月龄AL组大鼠的细胞。这些结果表明，短期热量限制会导致睾丸间质细胞功能受到抑制以及血清睾酮水平降低。与AL对照组相比，热量限制在25月龄大鼠中引起的血清睾酮浓度显著升高以及睾丸间质细胞睾酮生成增加，表明长期热量限制可以暂时抑制衰老所特有的类固醇生成减少。
