Chen H, Hardy M P, Huhtaniemi I, Zirkin B R
Department of Population Dynamics, Johns Hopkins University School of Hygiene and Public Health, Baltimore, Maryland.
J Androl. 1994 Nov-Dec;15(6):551-7.
Previous studies have demonstrated that Leydig cell testosterone production diminishes with age in Brown Norway rats. The objective of the studies presented herein was to test the following possible explanations for age-related decline in steroidogenesis: (1) decline in Leydig cell number; (2) understimulation by luteinizing hormone (LH); (3) reduced ability of individual Leydig cells to produce testosterone; and (4) influence of loss of germ cells. Leydig cells isolated from the testes of young and aged rats by centrifugal elutriation and Percoll density gradient centrifugation were examined for their ability to produce testosterone when stimulated maximally with LH or with dibutyryl cyclic AMP (dbcAMP). Leydig cell number and volume were examined in situ using stereological methods. Serum LH levels were measured using a highly sensitive immunofluorometric assay. Average Leydig cell volume decreased with age, and consistent with this observation, individual Leydig cells isolated from aging rats produced significantly less testosterone than those from young rats whether the cells were cultured in vitro with maximally stimulating LH or with dbcAMP. The age-associated diminished testosterone production could not be explained by changes in Leydig cell number, serum LH levels, Leydig cell responsiveness to LH, or testicular germ cell content. These results, taken together, suggest that the reduced testosterone production seen in aged rats is related to defects in the steroidogenic pathway beyond the LH receptor-cAMP cascade. The nature of the initial age-related changes that cause reduced steroidogenesis is not known, and therefore it is not known whether such changes are intrinsic or extrinsic to the Leydig cells.
先前的研究表明，在棕色挪威大鼠中，睾丸间质细胞产生睾酮的能力会随着年龄的增长而下降。本文所呈现的研究目的是检验以下关于类固醇生成随年龄下降的可能解释：（1）睾丸间质细胞数量减少；（2）促黄体生成素（LH）刺激不足；（3）单个睾丸间质细胞产生睾酮的能力降低；（4）生殖细胞丢失的影响。通过离心淘析和Percoll密度梯度离心从年轻和老年大鼠睾丸中分离出的睾丸间质细胞，在使用LH或二丁酰环磷腺苷（dbcAMP）进行最大程度刺激时，检测其产生睾酮的能力。使用体视学方法原位检测睾丸间质细胞的数量和体积。使用高度灵敏的免疫荧光测定法测量血清LH水平。平均睾丸间质细胞体积随年龄增长而减小，与此观察结果一致的是，无论这些细胞是在体外与最大刺激量的LH还是dbcAMP一起培养，从老年大鼠分离出的单个睾丸间质细胞产生的睾酮都明显少于年轻大鼠的细胞。睾丸间质细胞数量、血清LH水平、睾丸间质细胞对LH的反应性或睾丸生殖细胞含量的变化无法解释与年龄相关的睾酮产生减少。综合这些结果表明，老年大鼠中观察到的睾酮产生减少与LH受体 - cAMP级联反应之外的类固醇生成途径缺陷有关。导致类固醇生成减少的初始年龄相关变化的性质尚不清楚，因此也不清楚这些变化是睾丸间质细胞内在的还是外在的。
