Kobayashi S, Ishida A, Moriya H, Nogami H
Second Department of Internal Medicine, National Defense Medical College, Saitama, Japan.
Nephron. 1998 Dec;80(4):468-75. doi: 10.1159/000045221.
It is known that growth hormone (GH) contributes to glomerulosclerosis and that this probably occurs via insulin-like growth factor-I (IGF-I). However, the manner by which GH and nephrectomy (Nx) alter IGF-binding protein (IGFBP) mRNA in the kidney has not been fully explained. The effects of GH on renal IGF-I and IGFBP-1, 2, 3, 4, and 5 following Nx were examined in spontaneous dwarf rats (SDRs) which have a complete and specific lack of GH among pituitary hormones. In normal Sprague-Dawley rats (SDs), Nx resulted in significant decreases in levels of IGFBP-1 mRNA and IGFBP-5 mRNA to 62.7 +/- 4.9 and 56.5 +/- 5.0% those of sham-operated kidneys, respectively. Nx did not alter the IGF-I mRNA level in SDs. The levels of IGFBP-2, IGFBP-3, and IGFBP-4 mRNAs were likewise unchanged following nephrectomy. In SDRs, Nx significantly decreased the levels of IGFBP-1, IGFBP-4, and IGFBP-5 mRNA, to 57 +/- 2.6, 46 +/- 12, and 64 +/- 8.1% of sham-operated animals. However, Nx did not alter the levels of IGF-I, IGFBP-2, and IGFBP-3 mRNA. GH injections of nephrectomized SDRs fully normalized the decreased IGFBP-4 mRNA levels, whereas levels of IGFBP-1 and IGFBP-5 mRNA were not reversed. The altered expression of IGFBP-4 mRNA following Nx of SDRs compared to that of SDs appears highly significant since it is known that, unlike SDs, glomerulosclerosis does not fully develop in SDRs following renal ablation. The change in the IGFBP-4 mRNA level might be related to the development of glomerulosclerosis in SDs.
已知生长激素（GH）会导致肾小球硬化，这可能是通过胰岛素样生长因子-I（IGF-I）发生的。然而，GH和肾切除术（Nx）改变肾脏中IGF结合蛋白（IGFBP）mRNA的方式尚未完全阐明。在垂体激素中完全且特异性缺乏GH的自发性侏儒大鼠（SDR）中，研究了Nx后GH对肾脏IGF-I和IGFBP-1、2、3、4及5的影响。在正常的Sprague-Dawley大鼠（SD大鼠）中，Nx导致IGFBP-1 mRNA和IGFBP-5 mRNA水平显著降低，分别降至假手术肾脏水平的62.7±4.9%和56.5±5.0%。Nx并未改变SD大鼠中IGF-I mRNA水平。肾切除术后，IGFBP-2、IGFBP-3和IGFBP-4 mRNA水平同样未发生变化。在SDR中，Nx显著降低了IGFBP-1、IGFBP-4和IGFBP-5 mRNA水平，分别降至假手术动物的57±2.6%、46±12%和64±8.1%。然而，Nx并未改变IGF-I、IGFBP-2和IGFBP-3 mRNA水平。对肾切除的SDR注射GH可使降低的IGFBP-4 mRNA水平完全恢复正常，而IGFBP-1和IGFBP-5 mRNA水平并未恢复。与SD大鼠相比，SDR肾切除后IGFBP-4 mRNA表达的改变似乎非常显著，因为已知与SD大鼠不同，SDR肾切除后肾小球硬化不会完全发展。IGFBP-4 mRNA水平的变化可能与SD大鼠肾小球硬化的发展有关。
