CAJ | 학술논문

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组注射曲普瑞林,每2周1次,共2次;E2组在第2次曲普瑞林注射后每日注射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-3mRNA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),E2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-3mRNA、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GHR mRNA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.
목적 탐토단기(4주)촉성선격소석방격소의사물(GnRHa)대청춘기자성대서생장적영향급궤제.방법 40지3주령자서안수궤구조설계분위GnRHa처리조(Gn조)、자격소체대조(E2조)、대조조、란소절제조(OVX조)이급기선대조조.Gn조화E2조주사곡보서림,매2주1차,공2차;E2조재제2차곡보서림주사후매일주사E2공11d;OVX조재실험개시시여란소절제.제기선대조조외,소유서균재실험결속전9천화2천분별주사염산토매소화개황록소사기재골표면형성형광표기.비교4주후4조대서적체격생장지표、혈이도소양생장인자(IGF)-I급IGF결합단백(IGFBP)-3농도、간장생장격소수체(GHR)、IGF-I급IGFBP-3mRNA수평、경골생장판IGF-I급IGF-I수체(IGF-IR)수평、연골세포증식도등.결과 4주적GnRHa주사체도"성선절제"효응,Gn조적체중、신장、경골장도、생장판삼수、종향생장속솔、연골세포증식솔균교대조조증가(P<0.05혹P<0.01),E2조칙여대조조상근.4조적혈청IGF-I급IGFBP-3수평、간장IGF-I급IGFBP-3mRNA、생장판IGF-I급IGF-IR수평차이무통계학의의.Gn조화OVX조적간장GHR mRNA적표체균저우대조조,E2조칙여대조조상방.결론 GnRHa통과억제자격소적분비、간접촉진생장판연골세포증식도화억제생장판노화이촉진청춘기자서적선성생장,기촉생장효응불의뢰우IGF-I/IGFBP-3적내분비궤제,야불의뢰우생장판IGF-I/IGF-IR적개변.
Objective To investigate the possible mechanism of the effect of short-term gonadotropin-re-leasing 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 intramuscu-lar injections of 2.5mg·kg-1 triptorelin 2 weeks apart, and group E2 received additional daily 1μg·kg-1·d-1estradiol(E2)s. c. at three days after the second GnRHa injection for 11 days. Group Ctrl was sham-operated ascontrol. Each rat, except for the base-line control group. received 30mg/kg oxytetracycline s. c. and 20mg/kgcalcein 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-IR)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-IR in EGP.