Grzywacz F W, Chen H, Allegretti J, Zirkin B R
Division of Reproductive Biology, Johns Hopkins University, School of Hygiene and Public Health, Baltimore, MD 21205, USA.
J Androl. 1998 Sep-Oct;19(5):625-30.
Previous studies have shown that reductions in Leydig cell testosterone production occur with aging in the Brown Norway rat. The recent observation that changes in luteinizing hormone (LH) pulse interval and amplitude also occur with aging suggests the possibility that age-related reduced Leydig cell steroidogenesis might be related to changes in LH. We reasoned that, if this is the case, exogenously administered LH should restore testosterone production by aged rat Leydig cells to the higher levels produced by Leydig cells of young rats. To test this hypothesis, young (4-month-old) and aged (21-month-old) rats received testosterone- and estradiol-containing Silastic implants designed to suppress LH and, thus, endogenous Leydig cell testosterone production. At the same time, the rats received miniosmotic pumps programmed to deliver pulsatile ovine LH at a predetermined daily dose. In some experiments, treatment effects were determined by measuring testosterone production by testes perfused in vitro with maximally stimulating ovine LH. In others, Leydig cells were isolated by centrifugal elutriation and Percoll density gradient centrifugation, and their in vitro ability to produce testosterone in response to maximally stimulating LH was determined. Testes or isolated Leydig cells from untreated young rats produced about twice as much testosterone as that produced by Leydig cells from aged rats. The administration of testosterone- and estradiol-filled implants for 5 days reduced testosterone production significantly at both ages. In young rats administered 24 microg LH/day for 5 days, along with the implants, testosterone production was maintained at the high level of the young controls. Comparable treatment of aged rats resulted in testosterone production only at the low level of the aged controls. Indeed, even with higher LH doses (36 microg/day), testosterone production by the aged rat Leydig cells did not rise above the aged-control level. The inability of exogenously administered LH to increase testosterone production by testes and Leydig cells of aged rats suggests that Leydig cell steroidogenic deficits in the aged Brown Norway rat are unlikely to be the result of age-related changes in LH.
先前的研究表明，在雄性棕色挪威大鼠中，随着年龄增长，睾丸间质细胞的睾酮分泌量会减少。最近的观察结果显示，促黄体生成素（LH）脉冲间隔和幅度的变化也会随着年龄增长而出现，这表明与年龄相关的睾丸间质细胞类固醇生成减少可能与LH的变化有关。我们推测，如果情况确实如此，那么外源性给予LH应该能使老年大鼠睾丸间质细胞的睾酮分泌量恢复到年轻大鼠睾丸间质细胞所产生的较高水平。为了验证这一假设，对年轻（4个月大）和老年（21个月大）的大鼠植入含睾酮和雌二醇的硅橡胶植入物，以抑制LH，从而抑制内源性睾丸间质细胞睾酮的分泌。同时，给这些大鼠植入微型渗透泵，设定以预定的每日剂量输送脉冲式羊LH。在一些实验中，通过测量用最大刺激量的羊LH进行体外灌注的睾丸的睾酮分泌量来确定治疗效果。在其他实验中，通过离心淘洗和Percoll密度梯度离心分离睾丸间质细胞，并测定它们在体外对最大刺激量LH产生睾酮的能力。未处理的年轻大鼠的睾丸或分离出的睾丸间质细胞产生的睾酮量约为老年大鼠睾丸间质细胞产生量的两倍。给予含睾酮和雌二醇的植入物5天，两个年龄段的睾酮分泌量均显著降低。在植入物的同时，给年轻大鼠连续5天每天给予24微克LH，其睾酮分泌量维持在年轻对照的高水平。对老年大鼠进行类似治疗，其睾酮分泌量仅维持在老年对照的低水平。实际上，即使给予更高剂量的LH（36微克/天），老年大鼠睾丸间质细胞的睾酮分泌量也未超过老年对照水平。外源性给予LH无法增加老年大鼠睾丸和睾丸间质细胞的睾酮分泌量，这表明老年雄性棕色挪威大鼠睾丸间质细胞的类固醇生成缺陷不太可能是由与年龄相关的LH变化导致的。
