Protective effects of analogs of luteinizing hormone-releasing hormone against x-radiation-induced testicular damage in rats.
Protective effects of analogs of luteinizing hormone-releasing hormone against x-radiation-induced testicular damage in rats.
复制标题
黄体生成素释放激素类似物对 X 辐射引起的大鼠睾丸损伤的保护作用。
DOI：
10.1073/pnas.84.3.851
复制
发表时间：
1987
影响因子：
11.1
通讯作者：
Sampson,M
中科院分区：
文献类型：
--
作者：
Schally,AV;Paz-Bouza,JI;Schlosser,JV;Karashima,T;Debeljuk,L;Gandle,B;Sampson,M
研究了激动剂[D-Trp6]LH-RH（黄体生成素释放激素的类似物，Gly-6被d -色氨酸取代）和拮抗剂N-Ac-[D-Phe(pCI)1,2,D-Trp3,D-Arg6，D-Ala10]LH-RH对大鼠睾丸x射线损伤的保护作用。对照大鼠睾丸接受415或622拉德x射线照射3个月后，睾丸重量明显减轻，LH和促卵泡激素（FSH）水平升高，表明睾丸小管损伤。组织学研究表明，在给药415拉德的大鼠睾丸中，大多数精小管只有支持细胞而没有生发细胞，而在给药622拉德的组中，精子发生的抑制更为明显。用h - rh拮抗剂（每天1000微克/千克体重）预处理50天的大鼠，在415拉德后3个月睾丸重量和精子发生完全恢复，在622拉德后部分恢复，两组LH和FSH水平均恢复正常。因此，用rh - rh拮抗剂预处理大鼠，通过可逆地抑制性腺功能，保护睾丸的生殖细胞免受x射线的破坏作用。还进行了三个实验，给大鼠服用激动剂[D-Trp6] rh - rh长效微胶囊，每天释放25微克激动剂，预处理1-2个月。部分大鼠接受415或622拉德的性腺照射，恢复期2-4个月。尽管用[D-Trp6]LH- rh进行预处理，但与未照射对照组相比，照射组的睾丸重量明显降低，LH或FSH水平升高。精子发生恢复不完全，415拉德后生发细胞数量减少，尤其是622拉德后。根据睾丸重量、组织学和促性腺激素水平，可以得出结论，激动剂[D-Trp6]LH-RH对暴露于622拉德的大鼠睾丸没有保护作用，最多只能部分保护415拉德。这些结果表明，rh - rh拮抗剂和激动剂预处理可能会减轻辐射对睾丸的损伤，加速生殖功能的恢复。
Possible protective effects of the agonist [D-Trp6]LH-RH (analog of luteinizing hormone-releasing hormone in which Gly-6 is replaced by D-tryptophan) and antagonist N-Ac-[D-Phe(pCI)1,2,D-Trp3,D-Arg6,D-Ala10]LH-RH against testicular damage caused by x-radiation were investigated in rats. Three months after being subjected to x-irradiation of the testes with 415 or 622 rads, control rats showed marked reduction in the weights of the testes and elevated levels of LH and follicle-stimulating hormone (FSH), indicating tubular damage. Histological studies demonstrated that, in testes of rats given 415 rads, most seminiferous tubules had only Sertoli cells and no germinal cells, and, in the group given 622 rads, the depression of spermatogenesis was even more marked. Rats pretreated for 50 days with LH-RH antagonist (1000 micrograms/kg of body weight per day) showed a complete recovery of testicular weights and spermatogenesis 3 months after 415 rads and showed partial recovery after 622 rads, and LH and FSH levels returned to normal in both of these groups. Thus, pretreatment of rats with LH-RH antagonist, by reversibly inhibiting gonadal function, protected the germinal cells of the testes against damaging effects of x-rays. Three experiments were also carried out in which the rats were pretreated for 1-2 months with long-acting microcapsules of the agonist [D-Trp6]LH-RH, liberating 25 micrograms of the agonist per day. Some rats were then subjected to gonadal irradiation with 415 or 622 rads and allowed a recovery period of 2-4 months. In spite of pretreatment with [D-Trp6]LH-RH, testicular weights were significantly lower and LH or FSH levels were elevated in the irradiated groups as compared with nonirradiated controls. The recovery of spermatogenesis was incomplete, and there was a decrease in the number of germinal cells after 415 rads and especially after 622 rads. On the basis of testicular weights, histology, and gonadotropin levels, it could be concluded that the agonist [D-Trp6]LH-RH did not protect the rat testes exposed to 622 rads and, at most, only partially protected against 415 rads. These results suggest that pretreatment with LH-RH antagonists and possibly agonists, might decrease the testicular damage caused by radiation and accelerate the recovery of reproductive functions.