Mauras N, Rogol A D, Veldhuis J D
Nemours Children's Clinic, Jacksonville, Florida 32247.
J Clin Endocrinol Metab. 1989 Nov;69(5):1053-8. doi: 10.1210/jcem-69-5-1053.
To investigate the actions of acute and chronic low doses of ethinyl estradiol (EE) on the pulsatile characteristics of GH and gonadotropin release we studied seven girls with Turner's syndrome [mean age, 7.5 +/- 0.75 (+/- SE) yr] on 3 separate study days. At baseline (study I), blood was drawn every 20 min from 2000-0800 h for GH, LH, and FSH determinations. One month after study I the patients were started on 100 ng/kg EE, orally, daily, and an identical study was repeated 1 week (study II) and 5 weeks (study III) from the initiation of low dose EE therapy. A pulse detection algorithm, Cluster, was used to objectively analyze pulsatility profiles. There were consistent and significant increases in all seven patients after 5 weeks of low dose EE therapy in mean GH concentrations (study I, 7.0 +/- 1.1 micrograms/L; study III, 13.4 +/- 1.7; P = 0.008), mean area under the GH pulse (study I, 602 +/- 52 micrograms/L.min; study III, 1350 +/- 261; P = 0.026), and mean GH pulse amplitude (study I, 14.0 +/- 2.2 micrograms/L; study III, 32.8 +/- 6.0; P = 0.018); with no detectable changes in GH pulse frequency (study I, 5.3 +/- 0.6 pulses/12 h; study III, 5.3 +/- 0.4). These findings were not accompanied by any significant changes in plasma somatomedin-C or serum estradiol concentrations or urinary cytological maturation indexes. Conversely, the amount of radioimmunoassayable FSH activity was suppressed after low dose EE therapy, with a decrease in mean FSH concentrations (study I, 23.5 +/- 6.6 IU/L; study III, 5.9 +/- 1.2; P = 0.035) and mean pulse amplitude (study I, 28.6 +/- 8.6 IU/L; study III, 8.2 +/- 1.8; P = 0.038), with no detectable changes in FSH pulse frequency (study I, 7.6 +/- 0.6 pulses/12 h; study III, 7.3 +/- 0.6). Similar qualitative changes in LH pulsatility were observed after low dose estradiol administration. In conclusion, our results demonstrate that low dose EE therapy results in a significant augmentation of pulsatile GH activity, with reciprocal decreases in gonadotropin concentrations in girls with Turner's syndrome. Such observations indicate an exquisite sensitivity of gonadotrope and somatotrope function to low dose estrogen action in this prepubertal hypogonadal model.
为研究急性和慢性低剂量乙炔雌二醇（EE）对生长激素（GH）脉冲特性及促性腺激素释放的影响，我们在3个不同的研究日对7名特纳综合征女孩[平均年龄7.5±0.75（±标准误）岁]进行了研究。在基线期（研究I），于20:00至08:00每20分钟采集一次血样，测定GH、促黄体生成素（LH）和促卵泡生成素（FSH）。研究I结束1个月后，患者开始口服每日100 ng/kg的EE，并在开始低剂量EE治疗1周（研究II）和5周（研究III）后重复相同研究。使用一种脉冲检测算法Cluster客观分析脉冲性图谱。低剂量EE治疗5周后，所有7名患者的平均GH浓度（研究I，7.0±1.1μg/L；研究III，13.4±1.7；P = 0.008）、GH脉冲下的平均面积（研究I，602±52μg/L·min；研究III，1350±261；P = 0.026）和平均GH脉冲幅度（研究I，14.0±2.2μg/L；研究III，32.8±6.0；P = 0.018）均出现持续且显著的升高；而GH脉冲频率无明显变化（研究I，5.3±0.6次脉冲/12小时；研究III，5.3±0.4）。这些结果并未伴随血浆生长调节素-C、血清雌二醇浓度或尿细胞学成熟指数的任何显著变化。相反，低剂量EE治疗后可检测到的FSH活性量受到抑制，平均FSH浓度降低（研究I，23.5±6.6 IU/L；研究III，5.9±1.2；P = 0.035），平均脉冲幅度降低（研究I，28.6±8.6 IU/L；研究III，8.2±1.8；P = 0.038），FSH脉冲频率无明显变化（研究I，7.6±0.6次脉冲/12小时；研究III，7.3±0.6）。低剂量雌二醇给药后观察到LH脉冲性有类似的定性变化。总之，我们的结果表明，低剂量EE治疗可导致特纳综合征女孩的脉冲性GH活性显著增强，同时促性腺激素浓度呈相应降低。这些观察结果表明，在这个青春期前性腺功能减退模型中，促性腺激素细胞和生长激素细胞功能对低剂量雌激素作用具有极高的敏感性。
