EFFECTS OF AGING ON LEYDIG CELL STRUCTURE /FUNCTION AND SPERMATOGENESIS

健康棕色小鼠睾丸的最大容量 挪威大鼠产生的睾丸素随着年龄的增长显著下降。 该项目的长期目标是了解 这种下降背后的细胞内和细胞外机制， 及其后果。在第一部分，我们将确定年龄的影响 关于胆固醇在细胞内的运输 线粒体，并将其转化为孕烯醇酮。这个 衰老的间质细胞与缺乏黄体生成素的成年细胞的相似性表明 与年龄有关的黄体生成素使用受限的可能性。在第二部分，我们 将比较青少年和青少年间质中的黄体生成素水平 老年大鼠睾丸及外源性给予黄体生成素的能力 进入组织间隔室。我们将确定LH是否 会在体内和体外刺激老年间质细胞类固醇的生成。 使用相互的睾丸移植，我们还将确定 老年大鼠间质细胞的类固醇生成能力 移植到幼鼠体内后即可恢复。在第三部分中，我们将 检验假设，在去除旧的间质细胞后，用 EDS，~新~间质细胞重新填充了旧的测试。我们会 比较EDS后重新填充年轻和老年睾丸的细胞 关于细胞结构、促黄体生成素反应性、胆固醇 运输蛋白和类固醇生成酶。我们将决定 当新的间质细胞出现后成为 类固醇激素生成功能减退以了解 衰老动物产生的外在因素导致间质细胞 变得类固醇激素分泌功能减退，而不是 这种情况的发生与这些因素无关。在第四部分，我们将测试 以某种方式长期活跃的类固醇生成的假说 导致与年龄相关的类固醇合成减少，可能是通过 氧自由基。我们将确定是否慢性 抑制间质细胞类固醇合成将防止减少 类固醇合成。在相同的实验中，我们将确定 内源性类固醇合成的抑制是否会 抑制与年龄相关的生殖细胞丢失。

The maximal capacity of the testes of otherwise healthy Brown Norway rats to produce testosterone declines significantly with age. The long-term objectives of this project are to understand the intracellular and extracellular mechanisms that underlie this decline, and its consequences. In Part I, we will determine the effect of age on the intracellular transport of cholesterol to and into the mitochondria, and on its conversion to pregnenolone. The similarity of aged Leydig cells to LH-deprived adult cells suggests the possibility of age-related restricted access of LH. In Part II, we will compare LH levels in the interstitial compartment of young and old rat testes, and the ability of exogenously administered LH to enter the interstitial compartment. We will determine whether LH will stimulate steroidogenesis by old Leydig cells in vivo and vitro. Using reciprocal testicular transplants, we also will determine whether the steroidogenic abilities of Leydig cells from old rats can be restored when transplanted into young rats. In Part III, we will test the hypothesis that after the removal of old Leydig cells with EDS, ~new~ Leydig cells repopulate the old tests. We will compare the cells that repopulate young and old testes post-EDS with respect to cell structure, LH responsiveness, cholesterol transport proteins, and steroidogenic enzymes. We will determine when after their appearance the new Leydig cells become steroidogenically hypofunctional in order to understand whether extrinsic factors produced by aged animals cause Leydig cells to become steroidogenically hypofunctional, versus the possibility that this occurs independently of such factors. In Part IV, we will test the hypothesis that chronically active steroidogenesis in some way cause age-related reduced steroidogenesis, perhaps by producing oxygen free radicals. We will determine whether the chronic suppression of Leydig cells steroidogenesis will prevent reduced steroidogenesis. In the same experiments, we will determine whether the suppression of endogenous steroidogenesis will suppress age-related germ cell loss.