Miell J P, Buchanan C R, Norman M R, Maheshwari H G, Blum W F
Department of Medicine, King's College School of Medicine, London, UK.
J Endocrinol. 1994 Sep;142(3):547-54. doi: 10.1677/joe.0.1420547.
Inhibition of growth in man and laboratory animals by glucocorticoid treatment is well recognized, yet we have previously shown that glucocorticoids may paradoxically enhance GH secretion and increase serum insulin-like growth factor (IGF) levels. IGFs circulate bound to high-affinity binding proteins (IGFBPs) which modulate their actions, and circulating GH may be associated with two binding proteins (GHBPs) of which the high-affinity GHBP has been characterized and is structurally identical to the extracellular domain of the GH receptor. We have investigated the time-course of changes in GH, IGFs and their binding proteins induced by glucocorticoid treatment in normal male volunteers (n = 12, age range 22-31 years) sampled at 0800 h daily before and during treatment with dexamethasone (2 mg twice daily) for 5 days. In addition, subjects were sampled at 30-min intervals over 7-h periods (0730-1430 h) during the day prior to dexamethasone (day 0), on day 1 following the first dose of dexamethasone and on day 5 following the last dose of dexamethasone. Mean serum IGF-I rose over the initial 72 h and remained elevated at 96 h (297 +/- 11.5 compared with basal levels of 215.5 +/- 9.3 micrograms/l, P < 0.001) whereas IGF-II levels did not change (472.6 +/- 20.5 vs 450.3 +/- 21.7 micrograms/l, P = 0.97). There was a concomitant rise in serum IGFBP-3 from basal levels of 3.69 +/- 0.23 mg/l to a peak at 5 days of 4.16 +/- 0.21 (P = 0.003 vs day 1).(ABSTRACT TRUNCATED AT 250 WORDS)
糖皮质激素治疗对人和实验动物生长的抑制作用已得到充分认识,但我们之前已表明,糖皮质激素可能会自相矛盾地增强生长激素(GH)分泌并提高血清胰岛素样生长因子(IGF)水平。IGF以与高亲和力结合蛋白(IGFBP)结合的形式循环,这些结合蛋白调节其作用,而循环中的GH可能与两种结合蛋白(GHBP)相关,其中高亲和力GHBP已得到表征,其结构与GH受体的细胞外结构域相同。我们研究了地塞米松(每日2次,每次2 mg)治疗5天期间及之前,正常男性志愿者(n = 12,年龄范围22 - 31岁)每日08:00采样时,糖皮质激素治疗诱导的GH、IGF及其结合蛋白变化的时间进程。此外,在给予地塞米松前一天(第0天)、首次给予地塞米松后第1天以及最后一次给予地塞米松后第5天的白天7小时期间(07:30 - 14:30),每隔30分钟对受试者进行采样。血清IGF - I在最初72小时内升高,并在96小时时保持升高(297±11.5,而基础水平为215.5±9.3μg/L,P < 0.001),而IGF - II水平未变化(472.6±20.5 vs 450.3±21.7μg/L,P = 0.97)。血清IGFBP - 3从基础水平3.69±0.23 mg/L伴随升高,在第5天达到峰值4.16±0.21(与第1天相比,P = 0.003)。(摘要截断于250字)