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重组人促卵泡激素对促性腺激素释放激素拮抗剂处理大鼠精子发生维持的时间和阶段特异性影响

Temporal and stage-specific effects of recombinant human follicle-stimulating hormone on the maintenance of spermatogenesis in gonadotropin-releasing hormone antagonist-treated rat.

作者信息

Hikim A P, Swerdloff R S

机构信息

Division of Endocrinology, Harbor-UCLA Medical Center, Torrance 90509.

出版信息

Endocrinology. 1995 Jan;136(1):253-61. doi: 10.1210/endo.136.1.7828538.

DOI:10.1210/endo.136.1.7828538
PMID:7828538
Abstract

Despite considerable attention to the hormonal regulation of spermatogenesis, the role of FSH in adult mammals remains controversial. This is mainly due to the unavailability until recently of FSH preparations free of contaminating LH and discrepant results in various species. Using LH-free recombinant human FSH (rhFSH), we sought to determine if FSH is able to maintain spermatogenesis in rats in which both LH and FSH, but not other pituitary hormones, are markedly suppressed by GnRH-A treatment. Groups of five adult SD rats were given daily sc injections of vehicle, Nal-Glu-GnRH-A (1.25 mg/kg BW) or GnRH-A + 10 IU rhFSH for up to 4 weeks. In agreement with our previous report, GnRH-A treatment for 1 week led to a significant (P < 0.05) reduction in testis weight (26.6%) and in the number of specific germ cells involving preleptotene (27.7%) and pachytene spermatocytes (36.7%) and step 7 spermatids (30.3%) at stage VII of the seminiferous epithelial cycle. The number of advanced spermatids declined by 44.3%. Concomitant administration of rhFSH for 1 week resulted in a significant increase in testicular weight, tubular areas at stage VII-VIII, and in the absolute volumes of seminiferous tubules and their lumens compared to GnRH-A alone. Most importantly, FSH replacement to GnRH-A-treated rats fully attenuated the early (1 week) GnRH-A-induced reduction in germ cell numbers at stage VII as well as the number of advanced (steps 17-19) spermatids, and effectively prevented GnRH-A-induced reduction in the number of pachytene spermatocytes and step 7 spermatids for 2 weeks. In addition, FSH replacement to GnRH-A-treated rats was able to increase the number of B spermatogonia available for entry into meiosis and maintain the number of preleptotene spermatocytes throughout the treatment period. The observed beneficial effects of rhFSH on spermatogenesis in GnRH-A-treated rats are most likely not due to the stimulation of the Leydig cell function (via paracrine interaction between Sertoli and the Leydig cells), because FSH addition to GnRH-A had no discernible effect on intratesticular or plasma T levels, accessory organs weight, and the total volume of the Leydig cells when compared with GnRH-A alone.(ABSTRACT TRUNCATED AT 400 WORDS)

摘要

尽管对精子发生的激素调节已给予了相当多关注,但促卵泡激素(FSH)在成年哺乳动物中的作用仍存在争议。这主要是由于直到最近才获得不含促黄体生成素(LH)污染的FSH制剂,以及不同物种的结果存在差异。我们使用不含LH的重组人FSH(rhFSH),试图确定在经促性腺激素释放激素类似物(GnRH - A)处理后,LH和FSH(而非其他垂体激素)均被显著抑制的大鼠中,FSH是否能够维持精子发生。将五组成年SD大鼠每日皮下注射赋形剂、纳洛酮 - 谷氨酸 - GnRH - A(1.25 mg/kg体重)或GnRH - A + 10 IU rhFSH,持续4周。与我们之前的报告一致,GnRH - A处理1周导致睾丸重量显著(P < 0.05)降低(26.6%),以及在生精上皮周期VII期涉及前细线期(27.7%)、粗线期精母细胞(36.7%)和第7步精子细胞(30.3%)的特定生殖细胞数量减少。晚期精子细胞数量下降了44.3%。与单独使用GnRH - A相比,同时给予rhFSH 1周导致睾丸重量、VII - VIII期的管状区域以及生精小管及其管腔的绝对体积显著增加。最重要的是,对经GnRH - A处理的大鼠补充FSH完全减轻了早期(1周)GnRH - A诱导的VII期生殖细胞数量减少以及晚期(第17 - 19步)精子细胞数量减少,并有效防止了GnRH - A诱导的粗线期精母细胞和第7步精子细胞数量在2周内减少。此外,对经GnRH - A处理的大鼠补充FSH能够增加可进入减数分裂的B型精原细胞数量,并在整个治疗期间维持前细线期精母细胞数量。观察到的rhFSH对经GnRH - A处理大鼠精子发生的有益作用很可能不是由于对睾丸间质细胞功能的刺激(通过支持细胞与睾丸间质细胞之间的旁分泌相互作用),因为与单独使用GnRH - A相比,在GnRH - A中添加FSH对睾丸内或血浆睾酮水平、附属器官重量以及睾丸间质细胞的总体积没有明显影响。(摘要截断于400字)

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