Catalioto R M, Gaillard D, Ailhaud G, Négrel R
Centre de Biochimie du CNRS (UMR 134), U.F.R. Sciences, Laboratoire de Biologie du Développement du Tissu Adipeux, Université de Nice-Sophia Antipolis, France.
Growth Factors. 1992;6(3):255-64. doi: 10.3109/08977199209026932.
The role of growth hormone (GH) in the differentiation process of Ob1771 mouse preadipocyte cells has been studied under culture conditions that were serum-free and hormone-supplemented and which were previously shown to lead to terminal differentiation. In the absence of GH, a dramatic decrease in the adipogenic activity of the culture medium could be observed, as indicated 12 days after confluence by the low levels of glycerol-3-phosphate dehydrogenase activity and the sharp reduction of the number of triacylglycerol-containing cells. This decrease in adipogenic activity was accompanied by a parallel loss of the mitogenic potency of the culture medium. Determination of the half-maximal and maximal concentrations of GH required for the restoration of growth and differentiation were identical, 0.5 and 2 nM, respectively. Despite the presence of insulin-like growth factor-I (IGF-I) to substitute for supraphysiological concentrations of insulin and to saturate IGF-I receptor, GH was still required to induce terminal differentiation of a maximal number of cells. However, protein kinase C activators such as prostaglandin F2 alpha, phorbol esters and diacylglycerol were able to mimic GH in promoting a maximal mitogenic-adipogenic response, indicating that the ability of GH to induce diacylglycerol production (Doglio et al., 1989; Catalioto et al., 1990) plays a prominent role in this process. Furthermore, in agreement with the fact that the mitoses which precede terminal differentiation of Ob1771 preadipocytes are strictly controlled by cAMP and only modulated by protein kinase C, terminal differentiation of Ob1771 preadipocytes occurred in the absence of GH upon supplementation with high concentrations of carbaprostacyclin, added as a cAMP-elevating agent or with 8-Br-cAMP, added as a cAMP analogue. It is concluded that the control exerted by GH on terminal differentiation of mouse preadipocytes corresponds to a modulating mitogenic effect mediated through protein kinase C activation and leading to a potentiation of the cAMP and IGF-I mitogenic signalling pathways.
在无血清且添加激素的培养条件下，研究了生长激素（GH）在Ob1771小鼠前脂肪细胞分化过程中的作用。先前的研究表明，这种培养条件可导致细胞终末分化。在无GH的情况下，可观察到培养基的成脂活性显著降低，融合12天后，甘油-3-磷酸脱氢酶活性水平较低以及含三酰甘油细胞数量急剧减少即表明了这一点。成脂活性的降低伴随着培养基促有丝分裂能力的平行丧失。恢复生长和分化所需的GH半数最大浓度和最大浓度分别为0.5和2 nM，二者相同。尽管存在胰岛素样生长因子-I（IGF-I）来替代超生理浓度的胰岛素并使IGF-I受体饱和，但仍需要GH来诱导最大数量细胞的终末分化。然而，蛋白激酶C激活剂，如前列腺素F2α、佛波酯和二酰甘油，能够模拟GH促进最大的促有丝分裂-成脂反应，这表明GH诱导二酰甘油产生的能力（Doglio等人，1989年；Catalioto等人，1990年）在这一过程中起重要作用。此外，鉴于Ob1771前脂肪细胞终末分化之前的有丝分裂严格受cAMP控制且仅受蛋白激酶C调节，当添加作为cAMP升高剂的高浓度卡前列环素或作为cAMP类似物的8-溴-cAMP时，Ob1771前脂肪细胞在无GH的情况下也会发生终末分化。得出的结论是，GH对小鼠前脂肪细胞终末分化的控制对应于一种通过蛋白激酶C激活介导的调节性促有丝分裂作用，并导致cAMP和IGF-I促有丝分裂信号通路的增强。
