雌激素与C型利尿钠肽介导的青春期线性生长的关系

Relationship between estrogen and C-type natriuretic peptide-induced pubertal linear growth

目的:探讨青春期女孩雌激素与C型利尿钠肽(C-type natriuretic peptide,CNP)介导的长骨生长的关系,及两者在中枢性性早熟女孩GnRHa治疗相关身高增长减速中的作用。方法:(1)检测56例正常不同青春发育期女孩空腹血清雌二醇(E2)、CNP的N端前肽(N-terminal propeptide of CNP,NT-proCNP)、胰岛素样生长因子1(insulin-like growth factor 1,IGF-1)以及骨形成生化标志物N端中段骨钙素(N-terminal mid-fragment of osteocalcin,N-MID OC)的浓度。(2)检测13例特发性中枢性性早熟(idiopathic central precocious puberty,ICPP)女孩在促性腺激素释放激素类似物(gonadotropin-releasing hormone analogue,GnRHa)治疗开始、治疗6个月末及12个月末时血清E2、NT-proCNP、IGF-1和N-MID OC水平,并计算身高增长速度(height velocity,HV)。结果:(1)在56例正常不同青春发育期女孩中,与青春前期相比,血清NT-proCNP、IGF-1、E2和N-MID OC浓度均自青春早期开始升高(P<0.05或P<0.01);血清NT-proCNP在青春中期维持高水平,至青春后期达峰值(P<0.05);血清IGF-1和E2浓度于青春中期继续升高(P<0.01),亦至青春后期达峰值(P<0.01);血清N-MID OC浓度于青春中期达到峰值(P<0.05),青春后期则开始下降(P<0.05)。(2)ICPP女孩GnRHa治疗6个月末HV、血清NT-proCNP和血清N-MID OC均较治疗开始时显著下降(P<0.05),但与12个月末相比无显著差异;GnRHa治疗开始、治疗6个月末和12个月末后血清IGF-1浓度无显著差异;治疗后血清E2显著下降并回复至青春前期水平(P<0.05)。结论:女孩血清NT-proCNP水平随青春发育进程升高,与血清E2和IGF-1浓度平行,提示女孩青春期升高的雌激素在一定程度上可诱导CNP介导的青春期生长加速。ICPP女孩经GnRHa治疗后,随着雌激素受抑,生长速度减慢,血清NT-proCNP浓度下降,并与生长速度和骨形成平行,提示GnRHa致ICPP女孩生长减速部分缘于雌激素被抑制后CNP介导的长骨生长减慢。

AIM：To explore the association between estrogen and C-type natriuretic peptide （CNP）-induced endochondral ossification in pubertal girls, and to investigate the relationship between CNP signaling pathway and the gonadotropin-releasing hormone analogue （GnRHa）-associated linear growth reduction in girls with idiopathic central precocious puberty （ICPP）. METHODS：Serum levels of estradiol （E2）, N-terminal propeptide of CNP （NT-proCNP）, insulin-like growth factor 1 （IGF-1） and N-terminal mid-fragment of osteocalcin （N-MID OC） were measured in 56 healthy girls at different pubertal stages, and in 13 girls with ICPP at the beginning, the end of the 6th and 12th months of GnRHa treatment. Height velocity （HV） was also calculated. RESULTS：（1） Serum NT-proCNP, IGF-1, E2 and N-MID OC levels in the 56 healthy girls increased at early puberty compared with prepubertal levels （P〈0.05 or P〈0.01）. Serum NT-proCNP level remained high at middle puberty and peaked at late puberty （P〈0.05）. Serum IGF-1 and E2 levels continued to increase at middle puberty （P〈0.01） and peaked at late puberty （P〈0.01）. Serum N-MID OC level peaked at middle puberty （P〈0.05） and decreased at late puberty （P〈0.05）. （2） The HV and serum levels of NT-proCNP and N-MID OC in the 13 ICPP girls decreased at the end of the 6th month of GnRHa treatment compared with those at the beginning of GnRHa treatment （P〈0.05）, and remained low at the end of the 12th month of GnRHa treatment. Serum IGF-1 level at the end of the 6th and 12th months of GnRHa treatment remained as the same as that at the beginning. Serum E2 returned to the prepubertal level after GnRHa treatment （P〈0.05）. CONCLUSION：Serum NT-proCNP level increases across female pubertal process and peaks at late puberty, in parallel with serum E2 and IGF-1 levels. Elevated estrogen in female puberty may be associated with CNP-mediated adolescent growth spurt. Serum NT-proCNP level in ICPP girls decreases during GnRHa treatment, in parallel with linear growth velocity and bone formation. Linear growth reduction in girls with ICPP treated with GnRHa is partly due to decreased CNP-mediated long bone growth after estrogen inhibition.