Singh K, Ambler G R, Breier B H, Klempt M, Gluckman P D
Department of Pediatrics, University of Auckland, New Zealand.
Endocrinology. 1992 May;130(5):2758-66. doi: 10.1210/endo.130.5.1374015.
The somatogenic effects of recombinant ovine placental lactogen (oPL) were investigated in the GH-deficient dwarf rat and compared to those of identical doses of recombinant bovine GH (bGH) in three independent studies. Both oPL and bGH treatments resulted in an increase (P less than 0.05) in body weight gain compared to that in saline controls, with oPL treatment being more potent than bGH (P less than 0.05). In promoting linear growth, oPL was more potent (P less than 0.05) than bGH in some instances. The nitrogen content of dry carcass matter was increased with oPL treatment compared to saline (P less than 0.05), with a nonsignificant increase in bGH-treated animals. Carcass fat was similarly reduced by both oPL and bGH treatment (P less than 0.05) compared to saline. Serum insulin-like growth factor-I (IGF-I) concentrations were increased significantly (P less than 0.05) by both oPL and bGH treatments, with a significantly greater effect of oPL suggested in one study. No increase in hepatic IGF-I mRNA was evident with either treatment, suggesting that the increase in serum IGF-I is due to posttranscriptional mechanisms. The expression of IGF-binding protein-3 hepatic mRNA was increased (P less than 0.05) with bGH treatment compared to that after saline treatment, but was unaffected by oPL treatment, indicating regulation by GH at the transcriptional level. The binding of [125I]bGH to hepatic membrane preparations demonstrated no difference in specific binding compared to that in saline controls. However, [125I]oPL specific binding was greater in oPL-treated animals (P less than 0.05). Animals treated with bGH had reduced (P less than 0.05) hepatic GH receptor mRNA compared to saline controls, but oPL treatment had no effect. Thus, oPL is a potent anabolic and lipolytic agent in the dwarf rat, exerting greater somatogenic effects on some parameters than bGH. Our data suggest differences in receptor binding and effects on GH receptor and IGF-binding protein-3 expression with these two treatments, raising the possibility of actions through different pathways or differential effects at the GH receptor level.
在三项独立研究中,对生长激素缺乏型侏儒大鼠进行了重组绵羊胎盘催乳素(oPL)的躯体效应研究,并将其与相同剂量的重组牛生长激素(bGH)的效应进行了比较。与生理盐水对照组相比,oPL和bGH治疗均使体重增加(P<0.05),且oPL治疗比bGH更有效(P<0.05)。在促进线性生长方面,在某些情况下oPL比bGH更有效(P<0.05)。与生理盐水相比,oPL治疗使干胴体物质的氮含量增加(P<0.05),bGH治疗的动物增加不显著。与生理盐水相比,oPL和bGH治疗均使胴体脂肪减少(P<0.05)。oPL和bGH治疗均使血清胰岛素样生长因子-I(IGF-I)浓度显著增加(P<0.05),在一项研究中提示oPL的作用明显更强。两种治疗均未使肝脏IGF-I mRNA增加,提示血清IGF-I的增加是由于转录后机制。与生理盐水治疗后相比,bGH治疗使肝脏IGF结合蛋白-3 mRNA表达增加(P<0.05),但不受oPL治疗影响,表明生长激素在转录水平发挥调节作用。[125I]bGH与肝细胞膜制剂的结合显示,与生理盐水对照组相比,特异性结合无差异。然而,[125I]oPL在oPL治疗的动物中特异性结合更高(P<0.05)。与生理盐水对照组相比,bGH治疗的动物肝脏生长激素受体mRNA减少(P<0.05),但oPL治疗无影响。因此,oPL在侏儒大鼠中是一种有效的合成代谢和脂肪分解剂,在某些参数上比bGH具有更强的躯体效应。我们的数据表明,这两种治疗在受体结合以及对生长激素受体和IGF结合蛋白-3表达的影响方面存在差异,提示可能通过不同途径发挥作用或在生长激素受体水平产生不同效应。