Ungar H, Yaffe H, Livni N
Isr J Med Sci. 1975 Sep;11(9):867-76.
A threshold dose of ethionine was determined which, when administered continuously for up to 10 months, produced testicular lesions in rats but did not interfere with body growth and did not produce histologic lesions in the pancreas. In the liver, only mild fatty changes were observed. Interstitial cells of the testis showed hyperplasia at three to four months, followed by dedifferentiation of these cells in the later stages of the experiment. Complete atrophy of tubules was seen in most segments, but even at 8 and 10 months of ethionine ingestion, well-defined segments revealed intact spermatogenesis in all animals. The hypothetical emergence of a mutant ethionine-resistant spermatogonial stem cell is discussed. When ethionine was withdrawn from the diet at 10 months, incomplete regeneration of tubular epithelium was seen two months later, but the interstitial cells remained of the nondifferentiated type. Fatty changes in the liver, comparable to those observed in male ethionine-treated animals only after castration, are likely to have resulted from dedifferentiation of Leydig cells with concomitant testosterone deficiency. Rats receiving smaller doses of ethionine showed fatty change in the liver although no testicular lesions were recognizable. It is possible that ethionine interfered with synthesis of testosterone before testicular lesions could be demonstrated by light microscopy.
确定了乙硫氨酸的阈剂量，当连续给予大鼠长达10个月时，该剂量会导致大鼠睾丸病变，但不影响身体生长，也不会在胰腺中产生组织学病变。在肝脏中，仅观察到轻度脂肪变性。睾丸间质细胞在三到四个月时出现增生，在实验后期这些细胞随后发生去分化。在大多数节段中可见小管完全萎缩，但即使在摄入乙硫氨酸8个月和10个月时，所有动物的明确节段仍显示完整的精子发生。讨论了突变的抗乙硫氨酸精原干细胞的假设出现情况。当在10个月时从饮食中撤去乙硫氨酸时，两个月后可见小管上皮的不完全再生，但间质细胞仍为未分化型。肝脏中的脂肪变性，类似于仅在去势后在接受乙硫氨酸处理的雄性动物中观察到的情况，可能是由于Leydig细胞去分化并伴有睾酮缺乏所致。接受较小剂量乙硫氨酸的大鼠肝脏出现脂肪变性，尽管未发现睾丸病变。有可能在通过光学显微镜观察到睾丸病变之前，乙硫氨酸就干扰了睾酮的合成。
