Luo J M, Murphy L J
Department of Internal Medicine, Faculty of Medicine, University of Manitoba, Winnipeg, Canada.
Endocrinology. 1989 Jul;125(1):165-71. doi: 10.1210/endo-125-1-165.
Exogenous glucocorticoids are potent inhibitors of skeletal growth in experimental animals and children. The mechanism whereby glucocorticoids exert this effect is unclear, and circulating somatomedin levels have been reported to be low, normal, or high in this situation. Since recent studies have emphasized the importance of autocrine or paracrine insulin-like growth factor I (IGF-I), we have examined the effects of dexamethasone (DXM) on IGF-I gene expression in the hypophysectomized (hypox) and pituitary intact rat. An increase in IGF-I messenger RNA (mRNA) abundance of approximately 5-, 3-, 2-, and 1.5-fold in the liver, proximal tibia, lung, and kidney, respectively, was seen in hypox rats killed 6 h after injection of human GH (100 micrograms/100 g body wt). As little as 1 micrograms/100 g body wt of DXM administered 3 h before GH injection significantly reduced GH induction of IGF-I mRNA in the liver and the proximal tibia (P less than 0.05 and P less than 0.005, respectively). Higher doses of DXM were required to reduce IGF-I mRNA abundance in the kidney and lung. Of the tissues examined the order of sensitivity to DXM was liver greater than tibia greater than kidney greater than lung. In contrast to the effects of DXM on tissue IGF-I mRNA abundance, an approximately 10-fold higher dose of DXM was required to inhibit the GH-induced rise in serum IGF-I concentration. The effect of DXM on steady state IGF-I mRNA abundance in pituitary-intact rats which were killed 9 h after DXM was also examined. The reduction in IGF-I mRNA abundance required higher doses of DXM (6-360 micrograms/100 g body wt) and was less marked in pituitary-intact rats than in GH-treated hypox rats. In the pituitary-intact rats the order of sensitivity to DXM was tibia greater than liver greater than lung greater than kidney. In acute studies serum IGF-I levels were not decreased by any dose of DXM; rather a significant increase in serum IGF-I was apparent in pituitary intact rats, treated with the lowest and highest doses of DXM. When DXM was administered daily for 6 days to pituitary intact rats, body wt gain and hepatic and tibial IGF-I mRNA abundance were significantly reduced. No significant changes were seen in serum IGF-I concentrations.(ABSTRACT TRUNCATED AT 400 WORDS)
外源性糖皮质激素是实验动物和儿童骨骼生长的强效抑制剂。糖皮质激素发挥这种作用的机制尚不清楚，据报道在这种情况下循环生长调节素水平可低、正常或高。由于最近的研究强调了自分泌或旁分泌胰岛素样生长因子I（IGF-I）的重要性，我们研究了地塞米松（DXM）对垂体切除（hypox）和垂体完整大鼠IGF-I基因表达的影响。在注射人GH（100微克/100克体重）6小时后处死的hypox大鼠中，肝脏、胫骨近端、肺和肾脏中IGF-I信使核糖核酸（mRNA）丰度分别增加了约5倍、3倍、2倍和1.5倍。在GH注射前3小时给予低至1微克/100克体重的DXM可显著降低肝脏和胫骨近端中GH诱导的IGF-I mRNA水平（分别为P<0.05和P<0.005）。需要更高剂量的DXM才能降低肾脏和肺中IGF-I mRNA丰度。在所检查的组织中，对DXM的敏感顺序为肝脏>胫骨>肾脏>肺。与DXM对组织IGF-I mRNA丰度的影响相反，需要高约10倍剂量的DXM才能抑制GH诱导的血清IGF-I浓度升高。还研究了DXM给药9小时后处死的垂体完整大鼠中DXM对稳态IGF-I mRNA丰度的影响。IGF-I mRNA丰度的降低需要更高剂量的DXM（6-360微克/100克体重），并且在垂体完整大鼠中比在GH处理的hypox大鼠中不明显。在垂体完整大鼠中，对DXM的敏感顺序为胫骨>肝脏>肺>肾脏。在急性研究中，任何剂量的DXM均未降低血清IGF-I水平；相反，在用最低和最高剂量DXM处理的垂体完整大鼠中，血清IGF-I明显显著增加。当对垂体完整大鼠每日给予DXM 6天时，体重增加以及肝脏和胫骨IGF-I mRNA丰度显著降低。血清IGF-I浓度未见明显变化。（摘要截断于400字）
