Garibaldi L R, Aceto T, Weber C, Pang S
Department of Pediatrics, St. Louis University, Missouri 63104.
J Clin Endocrinol Metab. 1993 Apr;76(4):851-6. doi: 10.1210/jcem.76.4.8473395.
We used the GnRH agonist (GnRHa) stimulation test (20 micrograms/kg leuprolide sc, followed by 24-h serial sampling) to investigate the relationship between gonadotropin and estradiol (E2) secretion in the early phase of female central precocious puberty (CPP). Girls with CPP and moderately increased (early pubertal) peak E2 concentrations after GnRHa stimulation (136 +/- 11 pmol/L; range, 92-176; group B; n = 7) were compared to girls with CPP and higher (midpubertal) peak E2 responses to GnRHa (mean +/- SE, 590 +/- 63 pmol/L; range, 235-1189; group C; n = 19) and to a group of subjects with no breast development and a prepubertal hypothalamic-pituitary-gonadal axis (peak E2 response to GnRHa, 39 +/- 7 pM/L; range, 18-62; group A; n = 6). Compared to group A subjects, patients in group B had similar (P > 0.2) peak GnRHa-stimulated LH concentrations (B, 4.8 +/- 1 IU/L; A, 2.3 +/- 0.5 IU/L) and peak nocturnal LH (B, 0.81 +/- 0.2; A, 0.25 +/- 0 IU/L), but higher peak GnRHa-stimulated FSH concentrations (B, 26 +/- 7; A, 11 +/- 2 IU/L; P < 0.05) and mean nocturnal FSH (B, 4.2 +/- 1; A, 1.1 +/- 0.3 IU/L; P < 0.05) concentrations. Compared to group B, group C patients had higher (P < 0.001) GnRHa-stimulated peak LH (67 +/- 19 IU/L) and higher (P < 0.05) peak nocturnal LH (9.7 +/- 2.9 IU/L) concentrations, but similar GnRHa-stimulated peak FSH (27 +/- 3 IU/L) and mean nocturnal FSH (3.8 +/- 0.5 IU/L) levels. Group C patients with a ratio of peak GnRHa-stimulated LH to FSH concentrations below or above 1, respectively, had similar peak E2 responses to GnRHa (516 +/- 80 vs. 644 +/- 92 pM/L; P > 0.1). Stepwise regression analysis indicated that the peak LH response to GnRHa (r = 0.76; P < 0.001), but none of the FSH secretory parameters (P > 0.10), affected the E2 response to GnRHa. These data suggest that girls with CPP in the early phase of activation of the hypothalamic-pituitary-gonadal axis are capable of clinically relevant E2 production, which may occur in the face of low LH secretion and low LH/FSH ratios and cannot be explained solely on the basis of increased FSH secretion. Thus, endocrine or paracrine factors other than gonadotropins may be important in amplifying E2 secretion in the early phase of CPP.
我们采用促性腺激素释放激素激动剂（GnRHa）刺激试验（皮下注射亮丙瑞林20微克/千克，随后进行24小时连续采样）来研究女性中枢性性早熟（CPP）早期促性腺激素与雌二醇（E2）分泌之间的关系。将GnRHa刺激后E2峰值浓度中度升高（青春期早期）的CPP女孩（136±11皮摩尔/升；范围92 - 176；B组；n = 7）与GnRHa刺激后E2峰值反应更高（青春期中期）的CPP女孩（均值±标准误，590±63皮摩尔/升；范围235 - 1189；C组；n = 19）以及一组无乳房发育且下丘脑 - 垂体 - 性腺轴处于青春期前状态的受试者（GnRHa刺激后E2峰值反应，39±7皮摩尔/升；范围18 - 62；A组；n = 6）进行比较。与A组受试者相比，B组患者GnRHa刺激后的LH峰值浓度（B组，4.8±1国际单位/升；A组，2.3±0.5国际单位/升）和夜间LH峰值（B组，0.81±0.2；A组，0.25±0国际单位/升）相似（P>0.2），但GnRHa刺激后的FSH峰值浓度更高（B组，26±7；A组，11±2国际单位/升；P<0.05），夜间FSH均值也更高（B组，4.2±1；A组，1.1±0.3国际单位/升；P<0.05）。与B组相比，C组患者GnRHa刺激后的LH峰值（67±19国际单位/升）更高（P<0.001），夜间LH峰值（9.7±2.9国际单位/升）也更高（P<0.05），但GnRHa刺激后的FSH峰值（27±3国际单位/升）和夜间FSH均值（3.8±0.5国际单位/升）水平相似。GnRHa刺激后的LH与FSH峰值浓度之比分别低于或高于1的C组患者，GnRHa刺激后的E2峰值反应相似（516±80对644±92皮摩尔/升；P>0.1）。逐步回归分析表明，GnRHa刺激后的LH峰值反应（r = 0.76；P<0.001），而非FSH分泌参数中的任何一项（P>0.10），影响了GnRHa刺激后的E2反应。这些数据表明，下丘脑 - 垂体 - 性腺轴激活早期的CPP女孩能够产生具有临床意义的E2，这可能在LH分泌低和LH/FSH比值低的情况下发生，且不能仅基于FSH分泌增加来解释。因此，除促性腺激素外的内分泌或旁分泌因素可能在CPP早期放大E2分泌中起重要作用。
