Ren S G, Ezzat S, Melmed S, Braunstein G D
Division of Endocrinology & Metabolism, Cedars-Sinai Medical Center-UCLA School of Medicine 90048.
Endocrinology. 1992 Nov;131(5):2479-81. doi: 10.1210/endo.131.5.1385103.
As the somatostatin analog octreotide suppresses pituitary GH secretion and circulating IGF-1 levels, we examined its effects on human hepatoma (hep G2) cells which selectively express IGFBP-1. Octreotide (60 nM) stimulated IGFBP-1 up to 4.1-fold (p < 0.001 after 24 hrs). Induction of IGFBP-1 was first detectable after 12 hrs of 6 nM octreotide (1.5-fold, p < 0.03), and was confirmed by ligand blotting. Cholera toxin and forskolin induced IGFBP-1 independently and were also additive with octreotide. IGFBP-1 mRNA expression was induced 2.7-fold by octreotide. Thus, octreotide induces basal and stimulated IGFBP-1 in hepatocytes independently of insulin and GH. As IGFBP-1 may regulate peripheral IGF-1 action, induction of IGFBP-1 represents a novel pituitary-independent mechanism for octreotide action.
由于生长抑素类似物奥曲肽可抑制垂体生长激素分泌和循环中的胰岛素样生长因子-1(IGF-1)水平,我们研究了其对选择性表达IGFBP-1的人肝癌(hep G2)细胞的影响。奥曲肽(60 nM)可将IGFBP-1刺激至4.1倍(24小时后p < 0.001)。6 nM奥曲肽作用12小时后首次检测到IGFBP-1的诱导(1.5倍,p < 0.03),并通过配体印迹法得到证实。霍乱毒素和福斯高林可独立诱导IGFBP-1,且与奥曲肽具有相加作用。奥曲肽可使IGFBP-1 mRNA表达增加2.7倍。因此,奥曲肽可独立于胰岛素和生长激素在肝细胞中诱导基础和刺激状态下的IGFBP-1。由于IGFBP-1可能调节外周IGF-1的作用,IGFBP-1的诱导代表了奥曲肽作用的一种新的不依赖垂体的机制。