短期促性腺激素释放激素拟似物促进青春期雌性大鼠的线性生长  

Short-term long-acting gonadotropin-releasing hormone agonist accelerates longitudinal growth in female rats during puberty

作　　者：马华梅[1] 李燕虹[1] 苏喆[1] 杜敏联[1] 黄婷婷[1] 赖峰[1] 黄莲芳[2] 

机构地区：[1]广州中山大学附属第一医院儿科,510080 [2]广东医学院骨生物研究室

出　　处：《中华内分泌代谢杂志》2008年第3期248-253,共6页Chinese Journal of Endocrinology and Metabolism

摘　　要：目的探讨短期（4周）促性腺激素释放激素拟似物（GnRHa）对青春期雌性大鼠生长的影响及机制。方法40只3周龄雌鼠按随机区组设计分为GnRHa处理组（Gn组）、雌激素替代组（E2组）、对照组、卵巢切除组（OVX组）以及基线对照组。Gn组和E2组注射啦普瑞林，每2周1次，共2次；E2组在第2次曲普瑞林注射后每13注射E2共11d；OVX组在实验开始时予卵巢切除。除基线对照组外，所有鼠均在实验结束前9天和2天分别注射盐酸土霉素和钙黄绿素使其在骨表面形成荧光标记。比较4周后4组大鼠的体格生长指标、血胰岛素样生长因子（IGF）-Ⅰ及IGF结合蛋白（IGFBP）-3浓度、肝脏生长激素受体（GHR）、IGF—Ⅰ及IGFBP-3 mRNA水平、胫骨生长板IGF—Ⅰ及IGF—Ⅰ受体（IGF—ⅠR）水平、软骨细胞增殖度等。结果4周的GnRHa注射达到“性腺切除”效应，Gn组的体重、身长、胫骨长度、生长板参数、纵向生长速率、软骨细胞增殖率均较对照组增加（P〈0．05或P〈0．01），E：组则与对照组相近。4组的血清IGF—Ⅰ及IGFBP-3水平、肝脏IGF—Ⅰ及IGFBP-3 mRNA、生长板IGF—Ⅰ及IGF—ⅠR水平差异无统计学意义。Gn组和OVX组的肝脏GHRmRNA的表达均低于对照组，E2组则与对照组相仿。结论GnRHa通过抑制雌激素的分泌、间接促进生长板软骨细胞增殖度和抑制生长板老化而促进青春期雌鼠的线性生长，其促生长效应不依赖于IGF—Ⅰ／IGFBP-3的内分泌机制，也不依赖于生长板IGF—Ⅰ／IGF—ⅠR的改变。Objective To investigate the possible mechanism of the effect of short-term gonadotropin-releasing hormone agonist（GnRHa） on linear growth in female pubertal rats. Methods Forty 3-week-old female rats were randomly divided into 5 groups（ n = 8 each）. One group was sacrificed as base-line control. Group OVX was operated for ovariectomy at the beginning of experiment. Group Gn and group E2 each received two intramuscular injections of 2.5 mg · kg^-1 triptorelin 2 weeks apart, and group E2 received additional daily 1 μg · kg^-1· d^-1 estradiol （ E2 ） s.c. at three days after the second GnRHa injection for 11 days. Group Ctrl was sham-operated as control. Each rat, except for the base-line control group, received 30 mg/kg oxytetracycline s. c. and 20 mg/kg calcein s.c. 9 and 2 days respectively before sacrifice. Hepatic GH receptor mRNA, insulin-like growth factor （IGF）- Ⅰ and IGF binding protein （IGFBP）-3, circulating IGF- Ⅰ and IGFBP-3, local IGF- Ⅰ/IGF- Ⅰ receptor （IGF- Ⅰ R） and proliferation rate（PFR） in epiphyseal growth plate （EGP） were evaluated after 4-week treatment. Results Similar to group OVX, the rats in group Gn became taller and heavier than group Ctrl with greater tibial length, wider EGP, greater longitudinal growth rate（LGR） and higher PFR（ P 〈 0. 05 or P 〈 0.01 ）. Estrogen supplement reversed the effect of GnRHa. There was no statistical difference among the 4 groups regarding plasma IGF- Ⅰ and IGFBP-3, hepatic IGF-Ⅰ and IGFBP-3 mRNA levels, local IGF-Ⅰ and IGF-Ⅰ R levels in EGF. GnRHa down-regulated hepatic GHR mRNA expression, which was reversed by estrogen supplement. Conclusion GnRHa accelerates longitudinal growth of female pubertal rats. Estrogen deprivation contributes to GnRHa-induced alteration of linear growth in female rats, through improving PFR and suppressing the senescence of EGP. The underlying mechanism does not attribute to endocrine change of GH/IGF-Ⅰ axis or local IGF-Ⅰ/IGF- Ⅰ R in EGP.

关 键 词：青春期 骺生长板 促性腺激素释放激素拟似物 雌激素 

分 类 号：R585[医药卫生—内分泌]