Lue Y, Sinha Hikim A P, Wang C, Leung A, Baravarian S, Reutrakul V, Sangsawan R, Chaichana S, Swerdloff R S
Division of Endocrinology, Harbor-UCLA Medical Center, Torrance, California 90509, USA.
J Androl. 1998 Jul-Aug;19(4):479-86.
The antifertility effect of triptolide and other related compounds, isolated from Tripterygium wilfordii, has been demonstrated in male rats. The exact sites and mechanism of action of triptolide remain unknown. Our objectives were to determine whether triptolide at selected dose levels that induce infertility has any detrimental effects on the testes and to determine the sites and the possible mechanisms of its action. Groups of six adult male Sprague-Dawley rats were given oral administration of either vehicle (control group) or triptolide (50 or 100 microg/kg body weight) daily for 35 or 70 days. Body weight gain was normal in all treated groups. All six rats treated with a high dosage of triptolide were infertile during the second (63-70 days) mating trial. A lower dose (50 microg) of triptolide gave intermediate fertility values. Plasma levels of luteinizing hormone, follicle-stimulating hormone, testosterone, and intratesticular testosterone were not significantly different between control and triptolide-treated groups. Cauda epididymal sperm content was decreased by 68% and the motility, which averaged 58.2% in the control rat, was reduced to almost zero. No effects of triptolide were observed on testis and accessory organs weight, volumes of tubular lumen and the total Leydig cells, tubule diameter, and the number of Sertoli cells, spermatogonia, preleptotene (PL), and pachytene (P) spermatocytes. There were, however, modest but significant decreases in tubule volume and the number of round spermatids at stages VII-VIII. No changes in the germ cell apoptotic index measured at stages VII-VIII and XIV-I were noted between controls and rats rendered infertile with a high dose of triptolide. Thus, triptolide, at a dose level that induces complete infertility in the adult rats, has minimal adverse effects on the testes and acts primarily on the epididymal sperm making triptolide an attractive lead as a post-testicular male contraceptive.
从雷公藤中分离出的雷公藤内酯醇及其他相关化合物对雄性大鼠的抗生育作用已得到证实。雷公藤内酯醇的确切作用位点和作用机制尚不清楚。我们的目标是确定在诱导不育的选定剂量水平下，雷公藤内酯醇是否对睾丸有任何有害影响，并确定其作用位点和可能的作用机制。将六组成年雄性Sprague-Dawley大鼠分为三组，分别每日口服赋形剂（对照组）或雷公藤内酯醇（50或100微克/千克体重），持续35天或70天。所有处理组的体重增加均正常。在第二次（63 - 70天）交配试验期间，所有接受高剂量雷公藤内酯醇治疗的六只大鼠均不育。较低剂量（50微克）的雷公藤内酯醇产生中等的生育力值。对照组和雷公藤内酯醇处理组之间，促黄体生成素、促卵泡生成素、睾酮和睾丸内睾酮的血浆水平无显著差异。附睾尾部精子含量降低了68%，对照组大鼠精子平均活力为58.2%，而此时精子活力几乎降至零。未观察到雷公藤内酯醇对睾丸和附属器官重量、管腔体积、睾丸间质细胞总数、小管直径以及支持细胞、精原细胞、前细线期（PL）和粗线期（P）精母细胞数量有影响。然而，在VII - VIII期，小管体积和圆形精子细胞数量有适度但显著的减少。在VII - VIII期和XIV - I期测量的生殖细胞凋亡指数，对照组和用高剂量雷公藤内酯醇导致不育的大鼠之间未发现变化。因此，在能使成年大鼠完全不育的剂量水平下，雷公藤内酯醇对睾丸的不良影响最小，且主要作用于附睾精子，这使得雷公藤内酯醇成为一种有吸引力的睾丸后男性避孕药先导药物。
