Crave J C, Lejeune H, Brébant C, Baret C, Pugeat M
Laboratoire de la Clinique Endocrinologique, Hôpital de l'Antiquaille, Lyon, France.
J Clin Endocrinol Metab. 1995 Apr;80(4):1283-9. doi: 10.1210/jcem.80.4.7536204.
Changes in the plasma levels of corticosteroid-binding globulin (CBG) and sex hormone-binding globulin (SHBG) from birth to adulthood suggest that growth factors might influence clearance and/or hepatic secretion of CBG and SHBG in humans. The effects of insulin-like growth factor I (IGF-I) and insulin on CBG and SHBG synthesis by a clone of human hepatoblastoma-derived (Hep G2) cell lines were therefore investigated. The results showed that the immunoconcentrations of CBG and SHBG, as well as total protein concentration in culture medium from Hep G2 cells, were decreased by IGF-I and insulin. However, although the CBG-to-total protein ratio was decreased dose dependently by IGF-I and insulin, IGF-I and insulin did not dose-dependently decrease the SHBG-to-total protein ratio. The steady state levels of CBG and SHBG messenger RNAs (mRNAs) were reduced dose dependently by IGF-I with a half-effect at 5.4 +/- 1.9 and 4.6 +/- 1.6 nmol/L, respectively, and by insulin with a half-effect at 4.3 +/- 1.1 and 4.3 +/- 1.4 nmol/L, respectively. The maximum inhibitory effect of IGF-I on CBG mRNA level was 48 +/- 17% of control values and 60 +/- 13% for SHBG mRNA level. The changes in CBG mRNA levels were quantitatively similar to the changes in CBG immunoconcentration in the Hep G2 medium. In contrast, the inhibitory effects of insulin were only 17 +/- 8% and 31 +/- 12% of control values on CBG and SHBG mRNAs and 37 +/- 4% and 43 +/- 4% on CBG and SHBG concentrations, respectively. These results demonstrate that IGF-I reduces CBG and SHBG production by Hep G2 cells by decreasing mRNA steady state levels. The discrepancy between the inhibitory effects of insulin on CBG and SHBG mRNAs and protein secretion suggests that insulin exercises its inhibitory effects mainly on the mechanism(s) of translation and/or excretion of CBG and SHBG. The respective effects of IGF-I and insulin in the regulation of CBG and SHBG levels during fetal life and pubertal development in humans merit further study.
从出生到成年，血浆中皮质类固醇结合球蛋白（CBG）和性激素结合球蛋白（SHBG）水平的变化表明，生长因子可能影响人体中CBG和SHBG的清除及/或肝脏分泌。因此，研究了胰岛素样生长因子I（IGF-I）和胰岛素对人肝癌衍生（Hep G2）细胞系克隆合成CBG和SHBG的影响。结果显示，IGF-I和胰岛素降低了Hep G2细胞培养基中CBG和SHBG的免疫浓度以及总蛋白浓度。然而，尽管IGF-I和胰岛素使CBG与总蛋白的比率呈剂量依赖性降低，但IGF-I和胰岛素并未使SHBG与总蛋白的比率呈剂量依赖性降低。IGF-I使CBG和SHBG信使核糖核酸（mRNA）的稳态水平呈剂量依赖性降低，半数效应浓度分别为5.4±1.9和4.6±1.6 nmol/L，胰岛素使CBG和SHBG信使核糖核酸的稳态水平呈剂量依赖性降低，半数效应浓度分别为4.3±1.1和4.3±1.4 nmol/L。IGF-I对CBG mRNA水平的最大抑制作用为对照值的48±17%，对SHBG mRNA水平为60±13%。CBG mRNA水平的变化在数量上与Hep G2培养基中CBG免疫浓度的变化相似。相比之下，胰岛素对CBG和SHBG mRNA的抑制作用仅分别为对照值的17±8%和31±12%，对CBG和SHBG浓度的抑制作用分别为37±4%和43±4%。这些结果表明，IGF-I通过降低mRNA稳态水平减少Hep G2细胞产生CBG和SHBG。胰岛素对CBG和SHBG mRNA及蛋白分泌的抑制作用之间的差异表明，胰岛素主要通过翻译和/或CBG和SHBG排泄机制发挥其抑制作用。IGF-I和胰岛素在人类胎儿期和青春期发育过程中对CBG和SHBG水平调节的各自作用值得进一步研究。
