Bokser L, Szende B, Schally A V
Endocrine, Polypeptide and Cancer Institute, Veterans Administration Medical Center, New Orleans, LA 70146.
Br J Cancer. 1990 Jun;61(6):861-5. doi: 10.1038/bjc.1990.192.
The possible protective effect of an agonist of luteinising hormone-releasing hormone (LH-RH) against the ovarian damage caused by cyclophosphamide was investigated in rats. D-Trp6-LH-RH microcapsules were injected once a month for 3 months, in a dose calculated to release 25 micrograms day-1. Control animals received the injection vehicle. Sixty days after the first injection of microcapsules, cyclophosphamide was given at a loading dose of 50 mg kg-1 followed by 5 mg kg-1 day-1 for 30 days, while the treatment with D-Trp6-LH-RH was continued. When the ovaries were examined 3 months and 5 months after discontinuation of treatment, a significant reduction in the total number of follicles (P less than 0.01) was found in non-pretreated animals given cyclophosphamide. This reduction affected mainly follicles larger than 100 microns. An irreversible disintegration and destruction of granulosa cells was also observed in this group. In animals pretreated with D-Trp6-LH-RH, administration of cyclophosphamide caused no reduction in the number and diameter of follicles. Thus, the treatment with D-Trp6-LH-RH microcapsules before and during chemotherapy prevented the ovarian injury inflicted by cyclophosphamide. The suppression of gonadal function by LH-RH analogues could be possibly utilised for the protection of the ovaries against damage caused by cytotoxic drugs.
在大鼠中研究了促黄体生成素释放激素（LH-RH）激动剂对环磷酰胺所致卵巢损伤的可能保护作用。每月注射一次D-色氨酸6-LH-RH微胶囊，共3个月，剂量按每天释放25微克计算。对照动物注射溶媒。首次注射微胶囊60天后，给予环磷酰胺负荷剂量50毫克/千克，随后每天5毫克/千克，持续30天，同时继续用D-色氨酸6-LH-RH治疗。在停药3个月和5个月后检查卵巢时，发现给予环磷酰胺的未预处理动物的卵泡总数显著减少（P<0.01）。这种减少主要影响大于100微米的卵泡。在该组中还观察到颗粒细胞不可逆的崩解和破坏。在用D-色氨酸6-LH-RH预处理的动物中，给予环磷酰胺后卵泡数量和直径未减少。因此，化疗前和化疗期间用D-色氨酸6-LH-RH微胶囊治疗可预防环磷酰胺所致的卵巢损伤。LH-RH类似物对性腺功能的抑制作用可能可用于保护卵巢免受细胞毒性药物的损伤。
