Cotterill A M, Camacho-Hübner C, Holly J M, Savage M O
Department of Endocrinology, St Bartholomew's Hospital, London, UK.
Clin Endocrinol (Oxf). 1993 Jul;39(1):119-22. doi: 10.1111/j.1365-2265.1993.tb01761.x.
Growth hormone (GH) secretion is increased in conditions of GH insensitivity such as Laron syndrome, with elevation of both basal and peak levels. We have studied the effect of recombinant IGF-I therapy on the pattern of GH secretion in two subjects with GH insensitivity.
Two pubertal subjects with GH insensitivity (female, 16.4 years, breast stage 3; male 13.6 years, genital stage 2) were investigated after 6 months of IGF-I therapy (120 micrograms/kg twice daily s.c. at 0800 and 1900 h). GH profiles taken before the start of IGF-I therapy, when both subjects were prepubertal (aged 14.0 and 11.5 years respectively), were used for comparison.
GH profiles were performed with blood samples taken every 20 minutes between 2000 and 0800 h from an indwelling cannula.
Serum samples were assayed for GH by immunoradiometric assay and IGF-I, IGFBP-1 and insulin by radioimmunoassay.
Before IGF-I therapy, GH profile studies demonstrated pulsatile GH secretion. Basal GH was elevated with no value falling below the limit of detection of the assay and an increase in peak levels (maximum 203 and 206 mU/l at 0000 h and 0020 h respectively). After 6 months IGF-I therapy, the GH profiles were significantly different. With the onset of puberty a further increase in GH secretion would have been expected; nevertheless, following administration of IGF-I at 1900 h, GH secretion decreased with a reduction in mean overnight GH levels from 65 to 33 mU/l and 53 to 11 mU/l respectively. GH pulsatility was also suppressed in the two subjects, for the first 3.5 and 6 hours overnight respectively. Pulsatile GH secretion then returned with peak levels reaching 130 and 63 mU/l respectively. Prior to therapy IGF-I levels were at the lower limit of assay detection. On IGF-I therapy serum IGF-I levels reached a peak within 3 hours (298 and 438 micrograms/l) coinciding with the suppression of GH secretion. IGF-I levels fell rapidly overnight to 92 and 101 micrograms/l at 0800 h prior to the next injection. The fall in serum IGF-I coincided with the return of GH secretion. IGFBP-1 levels increased overnight both before and during IGF-I therapy, rising from 24 to 83 and 22 to 110 micrograms/l before therapy and 13 to 60 and 13 to 71 micrograms/l during therapy. This rise in IGFBP-1 appeared to be inversely related to the fall in serum insulin levels overnight and appeared not to be affected by IGF-I therapy.
GH secretion is suppressed by exogenous IGF-I therapy in GH insensitive subjects. The failure to maintain high serum IGF-I levels overnight, presumably due to a persisting defect in serum IGFBP-3 levels, was associated with an early return of GH secretion. These findings may have implications for the dose and regimen of IGF-I therapy in subjects with growth hormone insensitivity.
在生长激素不敏感的情况下，如拉伦综合征，生长激素（GH）分泌会增加，基础水平和峰值水平均会升高。我们研究了重组胰岛素样生长因子-I（IGF-I）治疗对两名生长激素不敏感受试者GH分泌模式的影响。
两名青春期生长激素不敏感受试者（女性，16.4岁，乳房发育3期；男性，13.6岁，生殖器发育2期）在接受IGF-I治疗6个月后（每天两次皮下注射120微克/千克，分别于08:00和19:00给药）接受了研究。将IGF-I治疗开始前（当时两名受试者均为青春期前，分别为14.0岁和11.5岁）采集的GH谱用于比较。
通过在20:00至08:00期间每隔20分钟从留置套管采集血样来进行GH谱分析。
采用免疫放射分析法测定血清样本中的GH，采用放射免疫分析法测定IGF-I、胰岛素样生长因子结合蛋白-1（IGFBP-1）和胰岛素。
在IGF-I治疗前，GH谱研究显示存在GH脉冲式分泌。基础GH升高，无值低于检测限，峰值水平增加（分别在00:00和00:20时最高达到203和206 mU/l）。在IGF-I治疗6个月后，GH谱有显著差异。随着青春期开始，预计GH分泌会进一步增加；然而，在19:00给予IGF-I后，GH分泌减少，平均夜间GH水平分别从65降至33 mU/l和从53降至11 mU/l。两名受试者的GH脉冲性也受到抑制，分别在夜间的前3.5小时和6小时。然后GH脉冲式分泌恢复，峰值水平分别达到130和63 mU/l。治疗前IGF-I水平处于检测限下限。在IGF-I治疗时，血清IGF-I水平在3小时内达到峰值（分别为298和438微克/升），与GH分泌受抑制同时出现。IGF-I水平在夜间迅速下降，在下一次注射前的08:00时分别降至92和101微克/升。血清IGF-I的下降与GH分泌的恢复同时出现。IGFBP-1水平在IGF-I治疗前和治疗期间的夜间均升高，治疗前从24升至83和从22升至110微克/升，治疗期间从13升至60和从13升至71微克/升。IGFBP-1的这种升高似乎与夜间血清胰岛素水平的下降呈负相关，且似乎不受IGF-I治疗的影响。
外源性IGF-I治疗可抑制生长激素不敏感受试者的GH分泌。夜间未能维持高血清IGF-I水平，推测是由于血清IGFBP-3水平持续存在缺陷，这与GH分泌的早期恢复有关。这些发现可能对生长激素不敏感受试者的IGF-I治疗剂量和方案有影响。
