Reinitiation of sperm production in gonadotropin-suppressed normal men by administration of follicle-stimulating hormone.
Reinitiation of sperm production in gonadotropin-suppressed normal men by administration of follicle-stimulating hormone.
复制标题
通过施用卵泡刺激素，促性腺激素抑制的正常男性重新启动精子产生。
DOI：
10.1172/jci111024
复制
发表时间：
1983
期刊：
影响因子：
--
通讯作者：
Bremner,WJ
中科院分区：
文献类型：
--
作者：
Matsumoto,AM;Karpas,AE;Paulsen,CA;Bremner,WJ
促黄体生成素（LH）和促卵泡激素（FSH）在控制人类精子发生中的具体作用知之甚少。我们研究了实验诱导的选择性LH缺乏对正常男性精子生成的影响。在3个月的对照期后，5名男性接受200 mg庚酸睾酮（T）i.m./ wk抑制LH、FSH和精子计数。然后，在以相同剂量继续T的同时，同时施用人FSH（hFSH）以替代FSH活性，使LH活性受到抑制。4名男性接受100 IU hFSH s.c.每日1次加T（高剂量hFSH）治疗13-14 wk，另1例用hFSH 50 IU皮下注射。每日1次加T（小剂量hFSH）治疗5 mo。在接受高剂量hFSH方案的4名男性中，单独给予T时精子计数明显受到抑制（0.3±0.2百万/cm 3，平均值±SE，而对照期为94±12百万/cm 3）。在单独使用T时，血清LH生物活性（通过体外小鼠Leydig细胞测定法测定）被抑制（140±7 ng/ml，而对照期间为375±65 ng/ml），FSH水平（通过放射免疫测定法测定）降至不可检测水平（<25 ng/ml，而对照期间为98±21 ng/ml）。添加100 IU hFSH皮下注射所有受试者的精子计数均显著增加（33±7百万/cm ~ 3，与单独T相比P< 0.02）。然而，没有受试者的精子计数始终在其对照范围内。在hFSH加T期间，所有四名男性的精子形态和活力均正常，两名男性的仓鼠卵体外精子穿透率正常。在高剂量hFSH给药期间，血清FSH水平升高至273±44 ng/ml（略高于FSH的正常范围，30-230 ng/ml）。血清LH生物活性与单独T给药期（147±9 ng/ml）相比无显著变化。在hFSH加T期后，所有四名男性在hFSH停止后继续单独接受T。精子计数再次受到严重抑制（0.2±0.1百万/cm 3），表明精子生成依赖于hFSH给药。与对照期相比，单独给予T期间血清T和雌二醇（E2）水平升高2 - 3倍。T和E2水平均保持不变，证实了hFSH制剂中缺乏显着的LH活性。在接受低剂量hFSH治疗的一名男子中，精子计数减少到严重的少精子水平，血清FSH被抑制到检测不到的水平，血清LH生物活性显着降低。加入50 IU hFSH s.c.每天至T，精子计数增加，平均为11±3百万/cm 3。在此期间，血清FSH水平升高至平均105±11 ng/ml（略高于该男性的对照范围，并在正常成人范围内），而LH生物活性仍受到抑制。在hFSH停止和单独T继续，精子计数再次严重减少到无精子症的水平。我们得出结论，FSH单独足以重新启动精子生产的人在促性腺激素抑制诱导外源性T管理。在这种情况下，FSH可能通过雄激素结合蛋白的产生增加睾丸内T或通过增加外源性T给药期间睾丸内T的生精反应敏感性来刺激精子产生。
The specific roles of luteinizing hormone (LH) and follicle-stimulating hormone (FSH) in controlling human spermatogenesis are poorly understood. We studied the effect of an experimentally induced, selective LH deficiency on sperm production in normal men. After a 3-mo control period, five men received 200 mg testosterone enanthate (T) i.m./wk to suppress LH, FSH, and sperm counts. Then, while continuing T at the same dosage, human FSH (hFSH) was administered simultaneously to replace FSH activity, leaving LH activity suppressed. Four men received 100 IU hFSH s.c. daily plus T (high dosage hFSH) for 13-14 wk, while one man received 50 IU hFSH s.c. daily plus T (low dosage hFSH) for 5 mo. The effect on sperm production of the selective LH deficiency produced by hFSH plus T administration was assessed.In the four men who received the high dosage hFSH regimen, sperm counts were markedly suppressed during T administration alone (0.3±0.2 million/cm3, mean±SE, compared with 94±12 million/cm3during the control period). Serum LH bioactivity (determined by in vitro mouse Leydig cell assay) was suppressd (140±7 ng/ml compared with 375±65 ng/ml during control period) and FSH levels (by radioimmunoassay) were reduced to undetectable levels (<25 ng/ml, compared with 98±21 ng/ml during control period) during T alone. With the addition of 100 IU hFSH s.c. daily to T, sperm counts increased significantly in all subjects (33±7 million/cm3,P< 0.02 compared with T alone). However, no subject consistently achieved sperm counts within his control range. Sperm morphology and motility were normal in all four men and in vitro sperm penetration of hamster ova was normal in the two men tested during the hFSH-plus-T period. During high-dosage hFSH administration, serum FSH levels increased to 273±44 ng/ml (just above the normal range for FSH, 30-230 ng/ml). Serum LH bioactivity was not significantly changed compared with the T-alone period (147±9 ng/ml). After the hFSH-plus-T period, all four men continued to receive T alone after hFSH was stopped. Sperm counts were again severely suppressed (0.2±0.1 million/cm3), demonstrating the dependence of sperm production on hFSH administration.Serum T and estradiol (E2) levels increased two- to threefold during T administration alone compared with the control period. Both T and E2levels remained unchanged with the addition of hFSH to T, confirming the lack of significant LH activity in the hFSH preparation.In the one man who received low dosage hFSH treatment, sperm counts were reduced to severely oligospermic levels, serum FSH was suppressed to undetectable levels, and serum LH bioactivity was markedly lowered during the T-alone period. With the addition of 50 IU hFSH s.c. daily to T, sperm counts increased, to a mean of 11±3 million/cm3. During this period, serum FSH levels increased to a mean of 105±11 ng/ml (slightly above this man's control range and within the normal adult range), while LH bioactivity remain suppressed. After hFSH was stopped and T alone was continued, sperm counts were again severely reduced to azoospermic levels.We conclude that FSH alone is sufficient to reinitiate sperm production in man during gonadotropin suppression induced by exogenous T administration. FSH may stimulate sperm production in this setting by increasing intratesticular T through androgenbinding protein production or by increasing the sensitivity of the spermatogenic response to the intratesticular T present during exogenous T administration.