Weinbauer G F, Behre H M, Fingscheidt U, Nieschlag E
Institute of Reproductive Medicine of the University, Munster, Germany.
Endocrinology. 1991 Oct;129(4):1831-9. doi: 10.1210/endo-129-4-1831.
The role of FSH in spermatogenesis was investigated in nonhuman primates depleted of testosterone by GnRH antagonist treatment. The GnRH antagonist antide (Nal-Lys; [N-acetyl-D-2-naphthyl-Ala1,D-4-chloro-Phe2,D-pyridyl-Ala3, nicotinyl-Lys5,D-nicotinyl-Lys6,isopropyl-Lys8,D-Ala10 ]-GnRH) was used at a daily dose of 450 micrograms/kg to suppress endogeneous gonadotropin and androgen production. Four groups of five cynomolgus monkeys (Macaca fascicularis) were subjected to the following treatment throughout a 16-week period: vehicle (group 1), GnRH antagonist (group 2), and GnRH antagonist plus human FSH (Fertinorm; 2 x 15 IU/day.animal; hFSH) during weeks 0-8 (group 3) or 8-16 (group 4). Testicular biopsies were performed before and after 4, 8, and 16 weeks of treatment. The tissue was analyzed by light microscopy and flow cytometry. Serum testosterone levels were suppressed into the range of orchidectomized animals in all GnRH antagonist-treated groups. In the absence of hFSH, serum inhibin levels were also markedly lowered. Concomitant administration of hFSH attenuated the GnRH antagonist-induced reduction of testicular size, while delayed treatment with hFSH failed to restimulate testicular volume. Numbers of A-dark spermatogonia, the reserve stem cells, were not altered by any of the treatments. hFSH either fully maintained or increased the counts for A-pale spermatogonia (renewing stem cells). The development of pachytene spermatocytes and round and elongated spermatids was markedly reduced or inhibited by the GnRH antagonist within 6-18 weeks. In contrasts, hFSH maintained these cell types at about 50% of baseline for 8 weeks. After 8 weeks of GnRH antagonist administration, hFSH stimulated A-pale spermatogonia and spermatocytes 2- to 3-fold with only minor effects on spermatid numbers. By means of flow cytometry, testicular cells were quantified according to DNA content. Within 8-16 weeks of GnRH antagonist treatment the percentage of 4C (mainly primary spermatocytes), 1C (round spermatids), and 1CC cells (elongated spermatids) had fallen from 65-75% to 5-25%. hFSH completely maintained the relative number of these cells, but failed to significantly restimulate the formation of 1CC cells.(ABSTRACT TRUNCATED AT 400 WORDS)
通过促性腺激素释放激素（GnRH）拮抗剂处理使睾酮缺乏的非人灵长类动物，研究了促卵泡激素（FSH）在精子发生中的作用。GnRH拮抗剂安替肽（Nal-Lys；[N-乙酰-D-2-萘基丙氨酸1、D-4-氯苯丙氨酸2、D-吡啶基丙氨酸3、烟酰-L-赖氨酸5、D-烟酰-L-赖氨酸6、异丙基-L-赖氨酸8、D-丙氨酸10]-GnRH）以每日450微克/千克的剂量使用，以抑制内源性促性腺激素和雄激素的产生。四组五只食蟹猴（猕猴）在16周的时间内接受了以下处理：溶剂（第1组）、GnRH拮抗剂（第2组），以及在第0 - 8周（第3组）或第8 - 16周（第4组）接受GnRH拮抗剂加人FSH（Fertinorm；2×15国际单位/天·动物；hFSH）。在处理4、8和16周之前和之后进行睾丸活检。通过光学显微镜和流式细胞术对组织进行分析。在所有接受GnRH拮抗剂处理的组中，血清睾酮水平被抑制到去势动物的范围内。在没有hFSH的情况下，血清抑制素水平也显著降低。同时给予hFSH可减轻GnRH拮抗剂诱导的睾丸大小减小，而延迟给予hFSH未能重新刺激睾丸体积。任何处理均未改变A暗型精原细胞（储备干细胞）的数量。hFSH要么完全维持要么增加A淡型精原细胞（更新干细胞）的数量。在6 - 18周内，GnRH拮抗剂显著减少或抑制了粗线期精母细胞以及圆形和长形精子细胞的发育。相比之下，hFSH在8周内将这些细胞类型维持在基线水平的约50%。在给予GnRH拮抗剂8周后，hFSH使A淡型精原细胞和精母细胞增加了2至3倍，对精子细胞数量的影响较小。通过流式细胞术，根据DNA含量对睾丸细胞进行定量。在GnRH拮抗剂处理的8 - 16周内，4C细胞（主要是初级精母细胞）、1C细胞（圆形精子细胞）和1CC细胞（长形精子细胞）的百分比从65 - 75%降至5 - 25%。hFSH完全维持了这些细胞的相对数量，但未能显著重新刺激1CC细胞的形成。（摘要截断于400字）
