Russell L D, Malone J P, Karpas S L
Tissue Cell. 1981;13(2):369-80. doi: 10.1016/0040-8166(81)90011-2.
A variety of agents (clomiphene citrate, cyproterone acetate, estradiol 17-beta, medrogestone, medroxyprogesterone, and methoxychlor) thought to disrupt the normal pathway by which hormones stimulate the testis were tested in rats to determine the early morphologic changes in the testis. After initial trial experiments at which dose and sacrifice intervals were determined, the earliest morphological abnormalities were assessed quantitatively and related to the particular spermatogenic stage in which these defects were initiated. All agents tested produced an identical morphological pattern of response displaying a significant increase in Stage VII degenerating cells (pachytene spermatocytes, step 7 and step 19 spermatids) as compared with vehicle-administered rats. The number of degenerating cells in other stages did not significantly change. The rise in degenerating cells in Stage VII, as seen in this study, was similar to that reported in Russell and Clermont (1972) utilizing hypophysectomized rats, and that reported by other investigators who have used a variety of agents to disrupt the hormonal stimulation of the seminiferous tubules. The data indicate that no matter how, or at what level the hormonal stimulation of the testis is interrupted, the morphological pattern of response is the same, and that such a pattern is useful in predicting the mechanism of action of agents suspected of interfering with hormone action.
人们认为多种药物(枸橼酸氯米芬、醋酸环丙孕酮、17-β-雌二醇、甲地孕酮、甲羟孕酮和甲氧滴滴涕)会干扰激素刺激睾丸的正常途径,为此在大鼠身上进行了测试,以确定睾丸早期的形态学变化。在确定了剂量和处死间隔的初步试验后,对最早出现的形态学异常进行了定量评估,并将其与这些缺陷开始出现时的特定生精阶段相关联。所有受试药物均产生了相同的形态学反应模式,与给予赋形剂的大鼠相比,VII期退化细胞(粗线期精母细胞、第7步和第19步精子细胞)显著增加。其他阶段的退化细胞数量没有明显变化。本研究中观察到的VII期退化细胞的增加,与Russell和Clermont(1972年)利用垂体切除大鼠所报告的情况以及其他使用多种药物干扰生精小管激素刺激的研究者所报告的情况相似。数据表明,无论睾丸的激素刺激是如何或在何种水平被中断,反应的形态学模式都是相同的,并且这种模式有助于预测怀疑干扰激素作用的药物的作用机制。