ETHYLENE DIMETHANESULFONATE DESTROYS LEYDIG-CELLS IN THE RAT TESTIS
ETHYLENE DIMETHANESULFONATE DESTROYS LEYDIG-CELLS IN THE RAT TESTIS
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DOI：
10.1210/endo-118-2-709
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发表时间：
1986-02-01
期刊：
影响因子：
4.8
通讯作者：
BARDIN, CW
中科院分区：
文献类型：
--
作者：
MORRIS, ID;PHILLIPS, DM;BARDIN, CW
本文研究了单剂量(100 mg/kg)抗生育化合物二甲基磺酸乙二醇酯(EDS)对成年大鼠睾丸间质细胞超微结构的影响。治疗12h后，大部分间质细胞出现变性改变。24注射后48h，所有间质细胞均出现明显变性改变。第4天和第14天，间质内未见完整的间质细胞。EDS治疗后第21天，可见细小的间质细胞，45天时，间质细胞正常。生精上皮在注射EDS后4d形态基本正常，但仍有轻微异常。第14天和第21天，生精上皮明显异常，48天，生精功能正常。治疗12、24和48小时后，在巨噬细胞胞浆内观察到大量物质，推测来自死亡的间质细胞。EDS后4d和14d，间质中以巨噬细胞为主。巨噬细胞胞浆内死亡的间质细胞内的包涵体几乎消失。睾丸匀浆中的黄体生成素受体(hCG结合)与间质细胞的细胞学变化相一致。受体浓度在24 h时较低，4天时几乎为零。这一变化伴随着血清睾酮水平在2天内下降到去势水平。根据血清FSH、LH和睾酮的监测，内分泌系统对EDS破坏间质细胞的反应慢于去势后的反应，表明对EDS的反应反映了杀死间质细胞所需的时间，而不是类固醇合成途径的直接损害。这些实验表明，间质细胞可以被一种细胞毒性药物特异性地摧毁。间质细胞特异性细胞毒剂的出现为进一步研究间质细胞和生精小管之间的相互关系提供了机会。
Untrastructural changes in the interstitial cells of the adult rat testis were studied up to 45 days after administration of a single dose (100 mg/kg) of the antifertility compound ethylene dimethanesulfonate (EDS). Most Leydig cells showed degenerative changes 12 h after treatment. Twenty-four and 48 h after injection, all Leydig cells observed showed gross degenerative changes. At 4 and 14 days, intact Leydig cells could not be identified in the interstitial spaces. Twenty-one days after treatment with EDS, small Leydig cells were visible, and at 45 days, Leydig cells appeared normal. The seminiferous epithelium appeared morphologically normal until 4 days after injection of EDS, when slight abnormalities were observed. At 14 and 21 days, the seminiferous epithelium was grossly abnormal, but at 48 days, spermatogenesis appeared normal. Twelve, 24, and 48 h after treatment, large quantities of material, presumably from dead Leydig cells, were observed within the macrophage cytoplasm. The predominant cell in the interstitial space 4 and 14 days after EDS was the macrophage. Inclusions from the dead Leydig cells within the cytoplasm of the macrophages had almost disappeared. LH receptors (hCG binding) in testicular homogenates were consistent with the cytological changes in Leydig cells. Receptor concentration was low at 24 h and was almost zero at 4 days. This change was accompanied by a decrease in serum testosterone to castrate levels by 2 days. The responses of the endocrine system to destruction of the Leydig cell by EDS, as monitored by serum FSH, LH, and testosterone, were slower than those after castration, indicating that the response to EDS reflects the time required to kill the Leydig cell rather than direct impairment of the steroidogenic pathway. These experiments demonstrate that Leydig cells can be specifically destroyed by a cytotoxic drug. The availability of a specific cytotoxic agent for Leydig cells offers further opportunities to study the interrelationships between the Leydig cell and the seminiferous tubule.