Chen H, Huhtaniemi I, Zirkin B R
Department of Population Dynamics, Johns Hopkins University School of Public Health, Baltimore, Maryland 21205, USA.
Endocrinology. 1996 Aug;137(8):3447-52. doi: 10.1210/endo.137.8.8754773.
The capacity of Brown Norway rat Leydig cells to produce testosterone has been shown to decrease with aging. Our objectives herein were to determine 1) whether ethane dimethanesulfonate (EDS) administration would eliminate the hypofunctional Leydig cells of the aged Brown Norway rat testis; 2) if so, whether a new generation of Leydig cells subsequently would appear; and 3) if so, whether the steroidogenic capacity of the new Leydig cells would be at the relatively low level of the cells they replaced or at the high level of young adult Leydig cells. Young (3-month-old) and aged (18-month-old) rats received an injection of EDS (8.5 mg/100 g BW). One, 5, and 10 weeks thereafter, the serum testosterone concentration and the capacity of the testes and of isolated Leydig cells to produce testosterone were determined. One week after EDS treatment, Leydig cells were not seen in the testes of young or aged rats, and the serum testosterone concentration and testicular testosterone production were reduced to undetectable levels. Five weeks after EDS treatment, serum testosterone levels at both ages were restored to those in age-matched controls, and the capacity of the testes to produce testosterone was restored partially (young rats) or completely (aged rats). By 10 weeks after EDS treatment, the serum testosterone concentration in young rats and the ability of their testes to produce testosterone were at the levels of age-matched controls. In aged rats, however, serum testosterone and testicular testosterone production were at levels that significantly exceeded those of aged-matched controls and, indeed, were not significantly different from those of young control or EDS-treated rats. Consistent with this, the ability of Leydig cells isolated from the testes of young rats and that of cells from aged rats to produce testosterone 10 weeks after the rats were treated with EDS were equivalent. The enhanced ability of the Leydig cells restored to the aged testes to produce testosterone was not a consequence of exposure to increased levels of LH. Thus, although situated in an aged testis and in the environment of an aged hypothalamic-pituitary axis, the steroidogenic function of the Leydig cells restored to aged rat testes was equivalent to that of young rat Leydig cells.
已证明棕色挪威大鼠的睾丸间质细胞产生睾酮的能力会随着衰老而下降。我们在此的目的是确定：1）给予乙烷二甲磺酸盐（EDS）是否会消除老年棕色挪威大鼠睾丸中功能减退的间质细胞；2）如果是这样，新一代的间质细胞随后是否会出现；3）如果是这样，新间质细胞的类固醇生成能力是处于它们所替代细胞的相对较低水平，还是处于年轻成年间质细胞的较高水平。年轻（3个月大）和老年（18个月大）大鼠接受EDS注射（8.5毫克/100克体重）。此后1周、5周和10周，测定血清睾酮浓度以及睾丸和分离的间质细胞产生睾酮的能力。EDS处理1周后，在年轻或老年大鼠的睾丸中未见到间质细胞，血清睾酮浓度和睾丸睾酮生成降至无法检测的水平。EDS处理5周后，两个年龄段的血清睾酮水平均恢复到年龄匹配对照组的水平，睾丸产生睾酮的能力部分恢复（年轻大鼠）或完全恢复（老年大鼠）。到EDS处理10周时，年轻大鼠的血清睾酮浓度及其睾丸产生睾酮的能力处于年龄匹配对照组的水平。然而，在老年大鼠中，血清睾酮和睾丸睾酮生成处于显著超过年龄匹配对照组的水平，实际上与年轻对照或EDS处理大鼠的水平无显著差异。与此一致的是，在大鼠接受EDS处理10周后，从年轻大鼠睾丸分离的间质细胞和从老年大鼠睾丸分离的细胞产生睾酮的能力相当。恢复到老年睾丸的间质细胞产生睾酮能力增强并非是由于暴露于升高水平的促黄体生成素（LH）。因此尽管位于老年睾丸中以及处于老年下丘脑 - 垂体轴的环境中，但恢复到老年大鼠睾丸的间质细胞的类固醇生成功能与年轻大鼠间质细胞的功能相当。
