Sjöberg A, Oscarsson J, Olofsson S O, Edén S
Department of Physiology, Göteborg University, Sweden.
Endocrinology. 1994 Oct;135(4):1415-21. doi: 10.1210/endo.135.4.7925103.
GH has previously been shown to regulate serum lipoprotein levels and hepatic secretion of apolipoprotein-B (apo-B) and apo-E in the rat. The aim of this investigation was to study a possible role of insulin-like growth factor-I (IGF-I) in this regulation. Adult female rats were hypophysectomized and treated with recombinant human IGF-I (1.25 mg/kg.day) as a sc continuous infusion for 7 days. The effects of IGF-I were compared with those of bovine GH, given either as a continuous sc infusion or as two daily sc injections. All hypophysectomized rats were given replacement therapy with L-T4 and cortisol. Serum IGF-I concentrations increased to similar levels as a result of treatment with bovine GH and IGF-I. There was no effect of IGF-I on serum concentrations of glucose or insulin, whereas GH, independent of its mode of administration, increased serum insulin concentrations. Food intake was not affected by treatment with IGF-I. IGF-I had no effect on serum concentrations of cholesterol or apo-E, whereas GH given twice daily decreased serum cholesterol concentrations, and a continuous infusion of GH increased serum apo-E concentrations. Serum triglyceride and apo-B concentrations increased markedly as a result of IGF-I treatment, whereas GH had no effect on serum triglycerides, but decreased serum apo-B concentrations. Hepatocytes were isolated from hypophysectomized rats treated with L-T4 and cortisol alone or in combination with IGF-I and kept in short term cultures. In this system, IGF-I had no effect on the incorporation of [3H]glycerol in triglycerides or the mass of triglycerides in the cells and medium. There was no effect of IGF-I treatment on the secretion of apo-E or apo-B. Moreover, there was no effect of IGF-I treatment on the relationship between newly synthesized and secreted apo-B 48 and apo-B 100, as determined by [35S]methionine labeling of the proteins. In conclusion, the previously observed effects of GH on serum lipoproteins and hepatic apolipoprotein secretion does not seem to be mediated via IGF-I, but IGF-I has its own unique effects on serum triglyceride and apo-B levels. The increases in serum apo-B and serum triglyceride concentrations after IGF-I treatment were not dependent on increased hepatic secretion of apo-B or triglycerides.
此前已有研究表明，生长激素（GH）可调节大鼠的血清脂蛋白水平以及载脂蛋白B（apo-B）和载脂蛋白E（apo-E）的肝脏分泌。本研究的目的是探讨胰岛素样生长因子-I（IGF-I）在该调节过程中可能发挥的作用。成年雌性大鼠接受垂体切除术后，以1.25毫克/千克·天的剂量皮下持续输注重组人IGF-I，为期一周。将IGF-I的作用与牛生长激素（bovine GH）进行比较，牛生长激素分别采用皮下持续输注或每日两次皮下注射的方式给药。所有垂体切除的大鼠均接受左甲状腺素（L-T4）和皮质醇替代治疗。牛生长激素和IGF-I治疗后，血清IGF-I浓度升高至相似水平。IGF-I对血清葡萄糖或胰岛素浓度无影响，而生长激素无论给药方式如何，均会使血清胰岛素浓度升高。食物摄入量不受IGF-I治疗的影响。IGF-I对血清胆固醇或apo-E浓度无影响，而每日两次注射生长激素可降低血清胆固醇浓度，持续输注生长激素则会增加血清apo-E浓度。IGF-I治疗后，血清甘油三酯和apo-B浓度显著升高，而生长激素对血清甘油三酯无影响，但会降低血清apo-B浓度。从仅接受L-T4和皮质醇治疗或联合IGF-I治疗的垂体切除大鼠中分离肝细胞，并进行短期培养。在该系统中，IGF-I对甘油三酯中[3H]甘油的掺入或细胞及培养基中甘油三酯的含量无影响。IGF-I治疗对apo-E或apo-B的分泌无影响。此外，通过蛋白质的[35S]甲硫氨酸标记测定，IGF-I治疗对新合成和分泌的apo-B 48与apo-B 100之间的关系无影响。总之，此前观察到的生长激素对血清脂蛋白和肝脏载脂蛋白分泌的影响似乎并非通过IGF-I介导，但IGF-I对血清甘油三酯和apo-B水平有其独特作用。IGF-I治疗后血清apo-B和血清甘油三酯浓度的升高并非依赖于肝脏apo-B或甘油三酯分泌的增加。
