Wilson M E, Tanner J M
Yerkes Primate Research Center, Emory University, Atlanta, Georgia 30322.
J Clin Endocrinol Metab. 1994 Aug;79(2):495-501. doi: 10.1210/jcem.79.2.7519192.
The present study tested the hypothesis that a reduction in serum GH during adolescence would result in slower growth and delayed puberty. Skeletal growth and maturation as well as indices of reproductive development were studied in juvenile female rhesus monkeys receiving a constant sc infusion of a somatostatin analog, Sandostatin, at a dose of approximately 4.50 micrograms/kg BW.day (Ssa; n = 6) and in untreated females (Con; n = 6) from 18 months of age through the luteal phase of the second ovulation. Although age at menarche was similar in Con and Ssa females, first ovulation was delayed significantly in Ssa females, such that the interval between menarche and first ovulation was significantly longer in Ssa females. Serum concentrations of GH, insulin-like growth factor-I (IGF-I), and IGF-binding protein-3 were reduced in Ssa females, particularly after menarche. Although changes in body weight were similar between Ssa and Con females, growth in height was significantly greater in Con females. Furthermore, peak growth velocity in height occurred at a significantly later age in SSa females, but at a similar degree of skeletal maturity. Serum insulin and glucose levels in response to iv glucose were similar in the two groups; however, fasting levels of serum glucose decreased significantly in both groups with advancing age, but the decrease was greater in Con. During the luteal phase of the first 2 ovulatory cycles, there were diminished serum progesterone in 16.7% (2 of 12) of the Con and 41.7% (5 of 12) of the Ssa females. Serum estradiol was significantly lower throughout the first 2 ovulatory cycles in Ssa females, whereas serum LH and IGF-I were similar to those in Con females. Multiple regression analyses revealed that age at menarche was best predicted from the amount of growth in height before menarche, whereas those females who had higher serum IGF-binding protein-3 levels before menarche had an earlier growth spurt, and those who grew faster had a shorter interval between menarche and first ovulation. These data indicate that treatment with a long-acting somatostatin analog, which produces a relative deficiency in the GH axis, slows growth and delays the tempo of puberty. The data suggest that this delay may be due to a reduction in gonadal sensitivity to LH.
青春期血清生长激素（GH）水平降低会导致生长减缓及青春期延迟。对18个月大至第二次排卵黄体期的幼年雌性恒河猴进行了研究，一组（Ssa；n = 6）持续皮下输注剂量约为每千克体重每日4.50微克的生长抑素类似物善龙（Sandostatin），另一组（Con；n = 6）为未治疗的雌性猴子。虽然Con组和Ssa组雌性初潮年龄相似，但Ssa组雌性首次排卵明显延迟，因此Ssa组雌性初潮至首次排卵的间隔显著更长。Ssa组雌性血清GH、胰岛素样生长因子-I（IGF-I）和IGF结合蛋白-3浓度降低，初潮后尤其明显。虽然Ssa组和Con组雌性体重变化相似，但Con组雌性身高增长显著更大。此外，Ssa组雌性身高的峰值生长速度出现的年龄显著更晚，但骨骼成熟程度相似。两组静脉注射葡萄糖后血清胰岛素和葡萄糖水平相似；然而，随着年龄增长，两组空腹血清葡萄糖水平均显著下降，但Con组下降幅度更大。在前两个排卵周期的黄体期，Con组16.7%（12只中的2只）和Ssa组41.7%（12只中的5只）的雌性血清孕酮降低。Ssa组雌性在头两个排卵周期中血清雌二醇显著更低，而血清促黄体生成素（LH）和IGF-I与Con组雌性相似。多元回归分析显示，初潮年龄最好根据初潮前身高增长幅度来预测，初潮前血清IGF结合蛋白-3水平较高的雌性生长突增更早，生长更快的雌性初潮至首次排卵的间隔更短。这些数据表明，使用长效生长抑素类似物进行治疗会导致GH轴相对缺乏，从而减缓生长并延迟青春期进程。数据表明这种延迟可能是由于性腺对LH的敏感性降低所致。
