Wilson M E
Yerkes Primate Research Center of Emory University, Lawrenceville, Georgia 30243, USA.
J Endocrinol. 1997 May;153(2):327-35. doi: 10.1677/joe.0.1530327.
The present study examined the effects of IGF-I on serum concentrations of IGF binding protein-3 (IGFBP-3) and GH and assessed how treatment with estradiol and IGF-I would stimulate adolescent growth in monkeys with normal pituitary function. In study I, ovariectomized, juvenile female rhesus monkeys (21 months of age; n = 6) received a bolus injection of IGF-I (1 mg/kg s.c.) and serum samples were collected periodically through 48 h. The consequential elevation in serum IGF-I resulted in a parallel increase in serum IGFBP-3 at 1 and 3 h after treatment with values returning to baseline by 7 h. In contrast, the elevation in serum IGF-I resulted in a significant decline in serum GH within 3 h of treatment. These data confirm that an elevation in IGF-I increases IGFBP-3 while simultaneously acting in a negative feedback capacity to inhibit GH. In study II, ovariectomized, juvenile female rhesus monkeys served either as controls (Con, n = 6) or received a constant s.c. infusion of IGF-I (300 micrograms/day; Igf, n = 6) from 13 through 32 months of age. At approximately 26 months, females entered an estradiol-treatment protocol in which they received alternating blocks of 3 weeks of estradiol followed by 3 weeks of no estradiol. As found in study I, the elevation in serum IGF-I resulted in a significant increase in serum IGFBP-3 throughout the study in Igf compared with Con females. Estradiol administration significantly increased serum IGF-I and IGFBP-3 levels in both groups. Although the nano-molar ratio of IGF-I to IGFBP-3 was consistently higher in Igf females, the magnitude of the change in IGF-I:IGFBP-3 following estradiol treatment was similar between groups. Finally, the age-dependent increase in serum GH was dampened in Igf compared with Con females and the increase in response to estradiol was less in Igf females. Although total growth in crown-rump length was similar in both groups, Igf females grew more prior to estradiol replacement while Con females grew more once estradiol treatment was initiated. In addition, skeletal maturity was advanced more quickly in Igf females once estradiol treatment had been initiated. These data suggest that, in female monkeys with normal pituitary function, IGF-I administration inhibits endogenous GH secretion but is capable of stimulating crown-rump growth. Although IGF-I increased serum levels of IGFBP-3, the increase was not proportional to the increase in serum IGF-I achieved by the treatment. These data would suggest that IGF-I may regulate the release of this binding protein but that GH may be required to maintain equi-molar proportions of IGF-I to IGFBP-3. In addition, the observation that serum concentrations of IGF-I were increased further in IGF-I-treated females by the administration of estradiol without a change in serum GH, suggests that estradiol has a direct effect on IGF-I synthesis and release independent of GH.
本研究检测了胰岛素样生长因子-I（IGF-I）对血清中IGF结合蛋白-3（IGFBP-3）和生长激素（GH）浓度的影响，并评估了雌二醇和IGF-I治疗如何刺激垂体功能正常的猴子青春期生长。在研究I中，对去卵巢的幼年雌性恒河猴（21月龄；n = 6）进行一次皮下注射IGF-I（1 mg/kg），并在48小时内定期采集血清样本。治疗后1小时和3小时，血清IGF-I相应升高，导致血清IGFBP-3平行增加，至7小时时恢复至基线水平。相反，血清IGF-I升高导致治疗后3小时内血清GH显著下降。这些数据证实，IGF-I升高会增加IGFBP-3，同时以负反馈方式抑制GH。在研究II中，去卵巢的幼年雌性恒河猴作为对照组（Con，n = 6），或从13月龄至32月龄接受皮下持续输注IGF-I（300微克/天；Igf，n = 6）。约26月龄时，雌性猴子进入雌二醇治疗方案，接受为期3周的雌二醇治疗和3周的无雌二醇治疗交替阶段。如研究I中所发现的，与Con组雌性猴子相比，在整个研究过程中，Igf组雌性猴子血清IGF-I升高导致血清IGFBP-3显著增加。两组中雌二醇给药均显著增加血清IGF-I和IGFBP-3水平。尽管Igf组雌性猴子中IGF-I与IGFBP-3的纳摩尔比始终较高，但雌二醇治疗后两组中IGF-I:IGFBP-3的变化幅度相似。最后，与Con组雌性猴子相比，Igf组雌性猴子血清GH随年龄增长的升高受到抑制，且对雌二醇的反应性增加较小。尽管两组中顶臀长度的总生长相似，但Igf组雌性猴子在雌二醇替代前生长较多，而Con组雌性猴子在开始雌二醇治疗后生长较多。此外，一旦开始雌二醇治疗，Igf组雌性猴子的骨骼成熟进展更快。这些数据表明，在垂体功能正常的雌性猴子中，给予IGF-I可抑制内源性GH分泌，但能够刺激顶臀生长。尽管IGF-I增加了血清IGFBP-3水平，但该增加与治疗所实现的血清IGF-I增加不成比例。这些数据表明IGF-I可能调节这种结合蛋白的释放，但可能需要GH来维持IGF-I与IGFBP-3的等摩尔比例。此外，观察到在IGF-I治疗的雌性猴子中，给予雌二醇后血清IGF-I浓度进一步升高，而血清GH无变化，这表明雌二醇对IGF-I的合成和释放有直接影响，独立于GH。
