Blacker C M, Ataya K M, Savoy-Moore R T, Subramanian M G, Mutchnick M G, Dunbar J C
Department of Obstetrics and Gynecology, Wayne State University, Detroit.
Acta Endocrinol (Copenh). 1991 Nov;125(5):581-9. doi: 10.1530/acta.0.1250581.
To evaluate the effects of a gonadotropin-releasing hormone agonist on non-reproductive systems, we administered [D-Leu6,Des-gly10]-GnRH ethylamide (leuprolide; 5 micrograms/day) for 21 days to female Sprague-Dawley rats. In Experiment 1, continuous infusion (Alzet minipumps sc) was compared to injection. Increased thymus and body weights and decreased estradiol and uterine weights were noted for both administration methods. Spleen weight increased only in rats treated by continuous infusion. Ovary, kidney and liver weights did not change. Only leuprolide-injected rats had elevated LH with decreased corticosterone and ACTH levels, possibly related to the injection process. Glucose, insulin, progesterone, FSH and corticosterone/ACTH were not different. In Experiment 2, intact and ovariectomized rats were implanted with minipumps delivering leuprolide or 0.9% NaCl. Body and thymus weights increased, whereas uterine weight and estradiol declined in both leuprolide-treated and ovariectomized rats. No synergism between leuprolide and ovariectomy was noted. Thymosin alpha 1, but not thymosin beta 4, increased in leuprolide-treated ovariectomized rats. Peripheral white blood cell count was elevated in leuprolide-treated intact rats and ovariectomized rats. In bone marrow, non-nucleated cell count declined in leuprolide-treated intact rats, contributing to the decreased total cell count in this group. Nucleated cell count was unaffected. Therefore, thymus weight gain was accompanied only in some cases by functional changes. Our results demonstrate that leuprolide affects non-reproductive systems, in a similar manner to ovariectomy. We suggest that such alterations may be due to the hypoestrogenic environment produced by leuprolide.
为评估促性腺激素释放激素激动剂对非生殖系统的影响，我们对雌性斯普拉格-道利大鼠连续21天给予[D-亮氨酸6，去甘氨酸10]-GnRH乙酰胺（亮丙瑞林；5微克/天）。在实验1中，比较了持续输注（皮下植入Alzet微型泵）和注射两种给药方式。两种给药方式均使胸腺和体重增加，雌二醇和子宫重量降低。仅持续输注治疗的大鼠脾脏重量增加。卵巢、肾脏和肝脏重量未改变。仅注射亮丙瑞林的大鼠促黄体生成素升高，皮质酮和促肾上腺皮质激素水平降低，这可能与注射过程有关。血糖、胰岛素、孕酮、促卵泡生成素和皮质酮/促肾上腺皮质激素无差异。在实验2中，对完整和去卵巢的大鼠植入输送亮丙瑞林或0.9%氯化钠的微型泵。亮丙瑞林治疗组和去卵巢大鼠的体重和胸腺重量均增加，而子宫重量和雌二醇均下降。未观察到亮丙瑞林与去卵巢之间的协同作用。亮丙瑞林治疗的去卵巢大鼠中胸腺素α1升高，但胸腺素β4未升高。亮丙瑞林治疗的完整大鼠和去卵巢大鼠外周白细胞计数升高。在骨髓中，亮丙瑞林治疗的完整大鼠无核细胞计数下降，导致该组总细胞计数减少。有核细胞计数未受影响。因此，仅在某些情况下胸腺重量增加伴随着功能变化。我们的结果表明，亮丙瑞林对非生殖系统的影响与去卵巢相似。我们认为这种改变可能是由于亮丙瑞林产生的低雌激素环境所致。
