Gurland G, Ashcom G, Cochran B H, Schwartz J
Department of Physiology, University of Michigan Medical School, Ann Arbor 48109.
Endocrinology. 1990 Dec;127(6):3187-95. doi: 10.1210/endo-127-6-3187.
To investigate early events in GH action, we examined whether GH altered the expression of c-fos and c-jun mRNA in 3T3-F442A cells. The rapid induction of these early response protooncogenes is one of the initial events in stimulation of cell proliferation and differentiation by a variety of growth factors. In 3T3-F442A preadipocytes, which differentiate in response to GH, treatment with GH for 15-30 min transiently increased the expression of c-fos and c-jun mRNA at GH concentrations in the physiological range (10-500 ng/ml). Both genes were superinduced by GH in the presence of cycloheximide. Nuclear run-on experiments indicated that the effect of GH on c-fos and c-jun occurred at the level of gene transcription, indicating that in the 3T3-F442A preadipocytes, GH acts similarly to other growth factors which induce c-fos and c-jun. Chronic preincubation with the phorbol ester phorbol 12-myristate 13-acetate interfered with the induction of c-fos by GH, suggesting that diacylglycerol and protein kinase C are involved in this effect of GH. Insulin-like growth factor-I and insulin were less effective than equimolar concentrations of GH in inducing c-fos expression. Taken together, these findings are consistent with coordinated expression of c-fos and c-jun playing an early role in responses to GH in 3T3-F442A cells.
为了研究生长激素（GH）作用的早期事件，我们检测了GH是否会改变3T3 - F442A细胞中c - fos和c - jun mRNA的表达。这些早期反应原癌基因的快速诱导是多种生长因子刺激细胞增殖和分化的初始事件之一。在对GH有反应而分化的3T3 - F442A前脂肪细胞中，用生理浓度范围（10 - 500 ng/ml）的GH处理15 - 30分钟会短暂增加c - fos和c - jun mRNA的表达。在放线菌酮存在的情况下，这两个基因都被GH超诱导。细胞核连续转录实验表明，GH对c - fos和c - jun的作用发生在基因转录水平，这表明在3T3 - F442A前脂肪细胞中，GH的作用类似于其他诱导c - fos和c - jun的生长因子。用佛波酯佛波醇12 - 肉豆蔻酸酯13 - 乙酸酯进行慢性预孵育会干扰GH对c - fos的诱导，这表明二酰基甘油和蛋白激酶C参与了GH的这一作用。胰岛素样生长因子 - I和胰岛素在诱导c - fos表达方面不如等摩尔浓度的GH有效。综上所述，这些发现与c - fos和c - jun的协同表达在3T3 - F442A细胞对GH的反应中起早期作用相一致。
