Bengtsson T, Cannon B, Nedergaard J
The Wenner-Gren Institute, The Arrhenius Laboratories F3, Stockholm University, S-106 91 Stockholm, Sweden.
Biochem J. 2000 May 1;347 Pt 3(Pt 3):643-51.
In brown adipocytes, fundamental cellular processes (cell proliferation, differentiation and apoptosis) are regulated by adrenergic stimulation, notably through beta-adrenergic receptors. The presence of all three beta-receptor subtypes has been demonstrated in brown adipose tissue. Due to the significance of the action of these receptors and indications that the subtypes govern different processes, the adrenergic regulation of the expression of the beta(1)-(,) beta(2)- and beta(3)-adrenoceptor genes was examined in murine brown-fat primary cell cultures. Moderate levels of beta(1)-receptor mRNA, absence of beta(2)-receptor mRNA and high levels of beta(3)-receptor mRNA were observed in mature brown adipocytes (day 6 in culture). Noradrenaline (norepinephrine) addition led to diametrically opposite effects on beta(1)- (markedly enhanced expression) and beta(3)-gene expression (full cessation of expression, as previously shown). beta(2)-Gene expression was induced by noradrenaline, but only transiently (<1 h). The apparent affinities (EC(50)) of noradrenaline were clearly different (7 nM for the beta(1)-gene and</=1 nM for the beta(3)-gene), as were the mediation pathways (solely via beta(3)-receptors and cAMP for the beta(1)-gene and via beta(3)-receptors and cAMP, as well as via alpha(1)-receptors and protein kinase C, for the beta(3)-gene). The half-lives of the corresponding mRNA species were very short but different (17 min for beta(1)-mRNA and 27 min for beta(3)-mRNA), and these degradation rates were not affected by noradrenaline, implying that the mRNA levels were controlled by transcription. Inhibition of protein synthesis also led to diametrically opposite effects on beta(1)- and beta(3)-gene expression, but - notably - these effects were congruent with the noradrenaline effects, implying that a common factor regulating beta(1)-gene expression negatively and beta(3)-gene expression positively could be envisaged. In conclusion, very divergent effects of adrenergic stimulation on the expression of the different beta-receptor genes were found within one cell type, and no unifying concept of adrenergic control of beta-receptor gene expression can be formulated, either concerning different cell types, or concerning the different beta-receptor subtype genes.
在棕色脂肪细胞中，基本细胞过程（细胞增殖、分化和凋亡）受肾上腺素能刺激调节，尤其是通过β-肾上腺素能受体。在棕色脂肪组织中已证实存在所有三种β-受体亚型。鉴于这些受体作用的重要性以及有迹象表明各亚型调控不同过程，我们在小鼠棕色脂肪原代细胞培养物中研究了β(1)、β(2)和β(3) -肾上腺素能受体基因表达的肾上腺素能调节。在成熟棕色脂肪细胞（培养第6天）中观察到β(1) -受体mRNA水平中等、β(2) -受体mRNA缺失以及β(3) -受体mRNA水平较高。添加去甲肾上腺素对β(1) -基因（表达显著增强）和β(3) -基因表达（如先前所示，表达完全停止）产生截然相反的影响。β(2) -基因表达由去甲肾上腺素诱导，但只是短暂诱导（<1小时）。去甲肾上腺素的表观亲和力（EC(50)）明显不同（β(1) -基因的为7 nM，β(3) -基因的≤1 nM），介导途径也不同（β(1) -基因仅通过β(3) -受体和cAMP，β(3) -基因则通过β(3) -受体和cAMP以及通过α(1) -受体和蛋白激酶C）。相应mRNA种类的半衰期非常短但不同（β(1) - mRNA为17分钟，β(3) - mRNA为27分钟），且这些降解速率不受去甲肾上腺素影响，这意味着mRNA水平受转录控制。抑制蛋白质合成也对β(1) -和β(3) -基因表达产生截然相反的影响，但值得注意的是，这些影响与去甲肾上腺素的影响一致，这意味着可以设想存在一个共同因子对β(1) -基因表达起负调节作用而对β(3) -基因表达起正调节作用。总之，在一种细胞类型中发现肾上腺素能刺激对不同β-受体基因的表达有非常不同的影响，并且无论是关于不同细胞类型还是关于不同β-受体亚型基因，都无法形成统一的肾上腺素能控制β-受体基因表达的概念。
