CNP在GH促进GnRHa治疗中大骨龄、青春中后期CPP/EFP女孩线性生长机制中的作用

 目的:探讨生长激素（growth hormone，GH）改善促性腺激素释放激素类似物（gonadotropin-releasing hormone analogue，GnRHa）治疗中大骨龄、青春中后期中枢性性早熟（central precocious puberty，CPP）或快速进展型早发育（early and fast puberty，EFP）女孩线性生长的近期疗效，以及C型利钠肽（C-type natriuretic peptide，CNP）在GH促线性生长机制中的作用。方法:22例骨龄≥11.5岁、预测成年身高（predicted adult height，PAH）严重受损、青春中后期的特发性CPP或EFP女孩分为2组各11例：（1）单用GnRHa组:仅用GnRHa（每4周缓释型曲普瑞林60～80 μg/kg,im）治疗；（2）联用GH组:联用GnRHa和GH（每周1 U/kg，分6~7次睡前sc）治疗。每3个月测量身高和体重，检查性征；治疗开始和治疗6个月末行骨龄检查，并检测血清CNP氨基端前体（amino-terminal pro-C-type natriuretic peptide，NTproCNP）、胰岛素样生长因子1（insulin-like growth factor 1，IGF-1）及1型前胶原氨基端伸展肽（procollagen type 1 amino-terminal propeptide，P1NP）的浓度。比较治疗前及治疗后6个月的身高增长速度（height velocity，HV)、按骨龄身高的标准差分值（height SD score for bone age，HtSDSBA）、PAH及上述血清指标的变化。结果:（1）联用GH组治疗6个月的HV、HtSDSBA增值（ΔHtSDSBA）和PAH增值（ΔPAH）均显著高于单用GnRHa组(P<0.01)。（2）联用GH组治疗6个月末与治疗开始时比较，血清NTproCNP、P1NP浓度和IGF-1浓度均无显著性差异。（3）单用GnRHa组治疗6个月末的血清NTproCNP和P1NP浓度则均较治疗开始时显著下降（P<0.05)，IGF-1浓度则无显著差异。结论: 对于大骨龄、青春中后期的特发性CPP或EFP女孩，GnRHa联用GH能促进线性生长，有效改善预测成年身高。GH的促生长作用不依赖于血清IGF-1水平的变化，而可能部分与CNP介导的长骨生长加速有关。

Effect of combined treatment with GnRHa and GH on linear growth in mid-and late pubertal girls at great bone ages with CPP or EFP and rela-tion to CNP signaling pathway

AIM:To investigate the effect of combined treatment with gonadotropin-releasing hormone analogue (GnRHa) and growth hormone (GH) on the linear growth in mid- and late pubertal girls at great bone ages with central precocious puberty (CPP) or early and fast puberty (EFP), and to determine the relation between C-type natriuretic peptide (CNP) signaling pathway and the accelerative effect of GH  on long bone growth in these girls. METHODS:Twenty-two girls were diagnosed as CPP or EFP, whose bone ages were older than 11.5 years with impaired predicted adult height (PAH), and divided into GnRHa treatment group (treated with GnRHa alone, slow-release of triptorelin 60~80 μg/kg every 4 weeks, im) and combined treatment group (treated with GnRHa and GH, 1 U/kg GH every week for 6~7 times, sc). The height, weight and pubertal stage were determined every 3 months. At the beginning and after 6 months of the treatment, the bone age was evaluated and the serum concentrations of amino-terminal pro-C-type natriuretic peptide (NTproCNP), insulin-like growth factor 1 (IGF-1) and procollagen type 1 amino-terminal propeptide (P1NP) were measured. Height velocity (HV), height SD score for bone age (HtSDSBA), PAH and the serum indexes mentioned above were compared at the beginning and the end of the treatment. RESULTS:After 6 months of the treatment, HV, ΔHtSDSBA and ΔPAH of the girls treated with GnRHa+GH were statistically higher than those of the girls given GnRHa alone (P<0.01). Serum concentrations of NTproCNP， P1NP and IGF-1 were not significantly different between the beginning and the end of the 6-month combined treatment. The girls treated with GnRHa alone showed a significant decrease in both serum NTproCNP and P1NP levels (P<0.05) and no significant change of serum IGF-1 level after 6 months of the treatment. CONCLUSION: In the CPP or EFP girls who are in mid- and late puberty and at great bone ages, the combined treatment with GnRHa and GH may accelerate linear growth and improve predicted adult height. This effect of GH is not attributed to the change of serum IGF-1 level, and may be related in part to the acceleration of CNP-mediated long bone growth.