Matsumoto A M, Karpas A E, Paulsen C A, Bremner W J
J Clin Invest. 1983 Sep;72(3):1005-15. doi: 10.1172/jci111024.
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/cm(3), mean+/-SE, compared with 94+/-12 million/cm(3) during 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/cm(3), 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/cm(3)), demonstrating the dependence of sperm production on hFSH administration. Serum T and estradiol (E(2)) levels increased two- to threefold during T administration alone compared with the control period. Both T and E(2) levels 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/cm(3). 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.
促黄体生成素（LH）和促卵泡激素（FSH）在控制人类精子发生过程中的具体作用尚不清楚。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名男性每周接受200mg庚酸睾酮（T）肌肉注射，以抑制LH、FSH和精子计数。然后，在继续给予相同剂量T的同时，同时给予人促卵泡激素（hFSH）以替代FSH活性，而LH活性仍被抑制。4名男性每天皮下注射100IU hFSH加T（高剂量hFSH），持续13 - - 14周，而1名男性每天皮下注射50IU hFSH加T（低剂量hFSH )，持续五个月。评估了hFSH加T给药产生的选择性LH缺乏对精子生成的影响。在接受高剂量hFSH方案的4名男性中，仅给予T时精子计数明显受到抑制（0.3±±0.2百万/cm³，平均值±±标准误，与对照期的94±±12百万/cm³相比）。血清LH生物活性（通过体外小鼠睾丸间质细胞测定法测定 )受到抑制（140±±7 ng/ml，与对照期的375±±65 ng/ml相比），且仅给予T时FSH水平（通过放射免疫测定法）降至无法检测的水平（<25 ng/ml ,与对照期的98±±21 ng/ml相比）。每天向T中添加皮下注射100IU hFSH后，所有受试者的精子计数均显著增加（33±± - 7百万/cm³，与仅给予T相比P < 0.02）然而，没有受试者的精子计数始终达到其对照范围内。所有4名男性的精子形态和活力均正常 , 在hFSH加T期间测试的两名男性仓鼠卵的体外精子穿透能力正常。在高剂量hFSH给药期间，血清FSH水平升至273±±44 ng/ml(略高于FSH的正常范围30 - - 230 ng/ml）。与仅给予T时期相比，血清LH生物活性没有显著变化（147±±9 ng/ml）。在hFSH加T时期后 , 停止hFSH后，所有4名男性继续仅接受T治疗。精子计数再次严重受到抑制（0.2±±0.1百万/cm³），表明精子生成依赖于hFSH给药。与对照期相比，仅给予T时血清T和雌二醇（E₂₂）水平增加了两到三倍 , 在T中添加hFSH后，T和E₂₂水平均未改变，证实hFSH制剂中缺乏显著的LH活性。在接受低剂量hFSH治疗的1名男性中，精子计数降至严重少精子水平 , 血清FSH被抑制至无法检测的水平 , 且仅给予T时期血清LH生物活性显著降低。每天向T添加皮下注射50IU hFSH后，精子计数增加，平均达到l1±±3百万/cm³。在此期间，血清FSH水平升至平均105±±ll ng/ml(略高于该男性的对照范围且在正常成人范围内），而LH生物活性仍受到抑制。停止hFSH并继续仅给予T后 , 精子计数再次严重降至无精子水平。我们得出结论，在由外源性T给药诱导的促性腺激素抑制期间，单独的FSH足以重新启动人类的精子生成。在这种情况下，FSH可能通过增加雄激素结合蛋白的产生来增加睾丸内T，或通过增加生精反应对外源性T给药期间存在的睾丸内T的敏感性来刺激精子生成。
