生长激素（GH）和胰岛素样生长因子-I（IGF-I）在大鼠脾脏中对IGF-I、IGF-I受体及IGF结合蛋白基因表达的调控作用

Role of GH and IGF-I in the regulation of IGF-I, IGF-I receptor and IGF binding protein gene expression in the rat spleen.

作者信息

Domené H M, Meidan R, Yakar S, Shen-Orr Z, Cassorla F, Roberts C T, LeRoith D

机构信息

Diabetes Branch, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, MD 20892.

出版信息

Regul Pept. 1994 Aug 4;52(3):215-26. doi: 10.1016/0167-0115(94)90056-6.

DOI:10.1016/0167-0115(94)90056-6

PMID:7528435

Abstract

To characterize the expression of the IGF-I system in the spleen and its role in spleen growth, we have studied the effect of hypophysectomy and the action of either GH or IGF-I treatment on the expression of several components of the IGF system in the rat. Female Sprague-Dawley rats were hypophysectomized (Hx) on postnatal day 50, and five animals each received twice-daily sc injections of saline, bovine GH (bGH; 84 micrograms/animal/day), or recombinant human IGF-I (rhIGF-I; 125 micrograms/animal/day) for 11 days. Compared to sham-operated controls, Hx animals exhibited a reduction in both body (192.6 +/- 5.6 g (mean +/- S.E.M.) vs. 268.6 +/- 6.0 g; P < 0.001) and spleen weights (0.42 +/- 0.03 g vs. 0.84 +/- 0.06 g; P < 0.001). The reduction in body and spleen weights in Hx animals was partially prevented by both bGH and rhIGF-I. Body weights were 234.2 +/- 5.3 g (P < 0.001) after bGH and 213.8 +/- 6.3 g (P < 0.05) after rhIGF-I. Spleen weights were 0.56 +/- 0.048 after bGH P < 0.01 and 0.53 +/- 0.05 g after rhIGF-I (P < 0.05). Serum GH and IGF-I levels were markedly reduced in Hx animals and bGH partially maintained IGF-I levels. Hypophysectomy reduced spleen IGF-I mRNA levels (30.6 +/- 7.5% of control values; P < 0.05) and this reduction was prevented by bGH (96.6 +/- 24.2%; NS) but not by rhIGF-I (39.9 +/- 5.0% NS vs. Hx). There were no changes in GH receptor or IGF-I receptor mRNA levels in Hx or bGH or rhIGF-I-treated animals. When IGF-I binding protein (IGFBP) mRNA levels were studied under these conditions, we found that IGFBP-1 mRNA was not detected in spleen; IGFBP-2 mRNA levels were reduced in Hx rats (67.9 +/- 7.4% of control values, P < 0.05) and bGH treatment prevented this reduction (95.5 +/- 12.2%, NS). IGFBP-3 mRNA levels were not affected by hypophysectomy or by bGH treatment, but were reduced in rhIGF-treated rats (69.6 +/- 3.0%, P < 0.05). On the other hand, IGFBP-4 mRNA levels were increased in Hx rats (136.4 +/- 15.9% of control values, P < 0.05) and bGH treatment prevented this increase.(ABSTRACT TRUNCATED AT 250 WORDS)

摘要

为了描述胰岛素样生长因子-I（IGF-I）系统在脾脏中的表达及其在脾脏生长中的作用，我们研究了垂体切除的影响以及生长激素（GH）或IGF-I治疗对大鼠IGF系统几个组分表达的作用。雌性斯普拉格-道利大鼠在出生后第50天接受垂体切除（Hx），每组5只动物，每天两次皮下注射生理盐水、牛GH（bGH；84微克/动物/天）或重组人IGF-I（rhIGF-I；125微克/动物/天），持续11天。与假手术对照组相比，Hx动物的体重（192.6±5.6克（平均值±标准误）对268.6±6.0克；P<0.001）和脾脏重量（0.42±0.03克对0.84±0.06克；P<0.001）均降低。bGH和rhIGF-I均可部分阻止Hx动物体重和脾脏重量的降低。bGH治疗后体重为234.2±5.3克（P<0.001），rhIGF-I治疗后体重为213.8±6.3克（P<0.05）。bGH治疗后脾脏重量为0.56±0.048克（P<0.01），rhIGF-I治疗后脾脏重量为0.53±0.05克（P<0.05）。Hx动物的血清GH和IGF-I水平显著降低，bGH可部分维持IGF-I水平。垂体切除降低了脾脏IGF-I mRNA水平（为对照值的30.6±7.5%；P<0.05），bGH可阻止这种降低（96.6±24.2%；无显著性差异），但rhIGF-I不能（与Hx组相比为39.9±5.0%，无显著性差异）。在接受Hx、bGH或rhIGF-I治疗的动物中，GH受体或IGF-I受体mRNA水平无变化。在这些条件下研究IGF-I结合蛋白（IGFBP）mRNA水平时，我们发现脾脏中未检测到IGFBP-1 mRNA；Hx大鼠中IGFBP-2 mRNA水平降低（为对照值的67.9±7.4%，P<0.05），bGH治疗可阻止这种降低（95.5±12.2%，无显著性差异）。垂体切除或bGH治疗对IGFBP-3 mRNA水平无影响，但rhIGF-I治疗的大鼠中IGFBP-3 mRNA水平降低（69.6±3.0%，P<0.05）。另一方面，Hx大鼠中IGFBP-4 mRNA水平升高（为对照值的136.4±15.9%，P<0.05），bGH治疗可阻止这种升高。（摘要截断于250字）