Department of Medicine, 0693, University of California, San Diego, 9500 Gilman Drive, La Jolla, California 92093-0693.
Integr Comp Biol. 2005 Jan;45(1):172-8. doi: 10.1093/icb/45.1.172.
Multicellular animals, which evolved about 700 to 1,000 myr ago, contain many of the genes found in yeast. Important for the evolution of multicellular animals were new pathways for intercellular signaling that regulated more complex physiological responses. Here we focus on the contribution to this process of lipophilic molecules that interact with nuclear receptors and the aryl hydrocarbon receptor, as well as enzymes that regulate the concentrations of these molecules. Both nuclear receptors and the aryl hydrocarbon receptor are found in invertebrates and vertebrates. We propose that environmental chemicals (xenobiotics) have been an important influence on the evolution of multicellular animals through a process involving the co-evolution of ligand-activated transcription factors and enzymes that detoxify xenobiotics. Indeed, this conversion of "xenobiotic swords" into "adaptive plowshares" contributed to the diverse physiology found in multicelluar animals. An important implication of this analysis is that enzymes as well as hormone receptors are vulnerable targets for endocrine disruptors. That is, some toxic chemicals act by inhibiting the enzymes that catalyze the formation or degradation of lipophilic signals, such as steroids, thus, disrupting hormone action.
多细胞动物大约在 700 到 1000 百万年前进化而来，它们含有许多在酵母中发现的基因。对于多细胞动物的进化来说，新的细胞间信号通路对于调节更复杂的生理反应非常重要。在这里，我们重点关注与核受体和芳香烃受体相互作用的亲脂性分子以及调节这些分子浓度的酶对这一过程的贡献。核受体和芳香烃受体都存在于无脊椎动物和脊椎动物中。我们提出，环境化学物质（外源性化学物质）通过涉及配体激活转录因子和解毒外源性化学物质的酶的共同进化过程，对多细胞动物的进化产生了重要影响。事实上，这种将“外源性化学物质之剑”转化为“适应性犁”，促成了多细胞动物多样化的生理学。这一分析的一个重要含义是，酶和激素受体都是内分泌干扰物的脆弱靶标。也就是说，一些有毒化学物质通过抑制催化亲脂性信号（如类固醇）形成或降解的酶而起作用，从而破坏激素作用。
