Gross K M, Matsumoto A M, Bremner W J
J Clin Endocrinol Metab. 1987 Apr;64(4):675-80. doi: 10.1210/jcem-64-4-675.
To test the hypothesis that the frequency of pulsatile LHRH stimulation can differentially control LH and FSH secretion in man, we administered low doses of LHRH in pulsatile fashion in several different regimens to men with idiopathic hypogonadotropic hypogonadism (IHH) and presumed endogenous LHRH deficiency. In study 1, four men with IHH received a constant amount of LHRH per day in three different frequencies. After an initial 7-day period of LHRH (5.0 micrograms every 2 h), the men received 2.5 micrograms every 1 h and 7.5 micrograms every 3 h, each for 4 days, in varying order. Frequent blood samples were obtained before LHRH administration and at the end of each regimen. Before LHRH administration, mean serum FSH and LH levels were low [28 +/- 3 (+/- SEM) and 6 +/- 2 ng/mL, respectively], and they increased into the normal adult male range during LHRH treatment. As the frequency of LHRH administration decreased from every 1 to 2 to 3 h, serum FSH levels progressively increased from 99 +/- 33 to 133 +/- 34 to 181 +/- 58 ng/mL (P less than 0.05). Serum LH levels (34 +/- 6, 33 +/- 6, and 34 +/- 5 ng/mL) were significantly higher than those before LHRH administration and did not differ significantly among the three regimens. Total serum testosterone (T), estradiol, and free T levels were increased by LHRH, but were not significantly different during the three regions of LHRH administration. In study 2, three men with IHH received the same amount of LHRH per dose, given in two different pulse frequencies; 2.5 micrograms LHRH were administered in frequencies of every 0.5 h and every 1.5 h, each for 4 days, in varying order. During the 0.5 h frequency, the mean serum FSH level was 42 +/- 13 ng/mL, and it rose to 80 +/- 19 ng/mL during the 1.5 h frequency (P less than 0.05). Corresponding mean serum LH levels were 25 +/- 5 and 27 +/- 4 ng/mL. Serum T and estradiol levels were not significantly different during the two LHRH regimens. We conclude that the frequency of LHRH stimulation can differentially control FSH and LH secretion by the human pituitary gland, and the pattern of hormonal stimulation may be a determinant of target organ response.
为验证脉冲式促性腺激素释放激素(LHRH)刺激频率可不同程度地控制男性促黄体生成素(LH)和促卵泡生成素(FSH)分泌这一假说,我们以几种不同方案,对特发性低促性腺激素性性腺功能减退(IHH)且推测存在内源性LHRH缺乏的男性,采用脉冲式方式给予低剂量LHRH。在研究1中,4名IHH男性每天接受恒定剂量的LHRH,但频率不同。在最初7天给予LHRH(每2小时5.0微克)后,这些男性分别以每1小时2.5微克和每3小时7.5微克的频率各接受4天,顺序不同。在给予LHRH前及每个方案结束时采集频繁的血样。给予LHRH前,血清FSH和LH的平均水平较低[分别为28±3(±标准误)和6±2纳克/毫升],在LHRH治疗期间升至正常成年男性范围。随着LHRH给药频率从每1小时降至每2小时再降至每3小时,血清FSH水平从99±33逐渐升至133±34再升至181±58纳克/毫升(P<0.05)。血清LH水平(34±6、33±6和34±5纳克/毫升)显著高于给予LHRH前,且在三种方案间无显著差异。血清总睾酮(T)、雌二醇和游离T水平因LHRH而升高,但在LHRH给药的三个阶段无显著差异。在研究2中,3名IHH男性每次接受相同剂量的LHRH,但脉冲频率不同;以每0.5小时和每1.5小时的频率给予2.5微克LHRH,各持续4天,顺序不同。在每0.5小时的频率阶段,血清FSH平均水平为42±13纳克/毫升,在每1.5小时的频率阶段升至80±19纳克/毫升(P<0.05)。相应的血清LH平均水平分别为25±5和27±4纳克/毫升。在两种LHRH方案期间,血清T和雌二醇水平无显著差异。我们得出结论,LHRH刺激频率可不同程度地控制人垂体分泌FSH和LH,且激素刺激模式可能是靶器官反应的一个决定因素。