Cooke Paul S, Selvaraj Vimal, Yellayi Srikanth
Department of Veterinary Biosciences, University of Illinois, Urbana, 61802, USA.
J Nutr. 2006 Mar;136(3):704-8. doi: 10.1093/jn/136.3.704.
Estrogen regulates thymic development and immune function. Despite the critical role of estrogens in inducing thymic involution and modulating immune responses, the mechanism of this effect is unclear. Similarly, humans and animals are exposed to increasing amounts of the estrogenic soy isoflavone genistein in the diet, but whether genistein can induce immune changes has not been definitively established. We reported previously that genistein induces thymic atrophy in mice, and decreases both humoral and cell-mediated immunity. These thymic effects of genistein occur via estrogen receptor (ER)-mediated and non-ER-mediated pathways. Genistein injections produced the most pronounced effects, but dietary administration to mice that produced serum genistein concentrations similar to those reported in human infants consuming soy formula also had demonstrable effects. Microarray analysis of the effects of estradiol and genistein on neonatal thymus indicated that estradiol affected genes involved in transcription, apoptosis, cell cycle, and thymic development and function; genistein had similar effects on many estradiol target genes, but also had unique actions not replicated by estradiol. Despite extensive work showing inhibitory effects of genistein on immunity, other rodent studies reported that genistein or other phytoestrogens stimulate various aspects of immune function. Although the present data strongly indicate that genistein can regulate immune function, possibly at physiologic concentrations, further work is required to definitively establish overall thymic and immune effects of genistein and soy, which may vary with age, species, and specific end point.
雌激素调节胸腺发育和免疫功能。尽管雌激素在诱导胸腺退化和调节免疫反应中起着关键作用，但其作用机制尚不清楚。同样，人类和动物在饮食中接触到越来越多的具有雌激素活性的大豆异黄酮染料木黄酮，但染料木黄酮是否能引起免疫变化尚未明确确定。我们之前报道过，染料木黄酮可诱导小鼠胸腺萎缩，并降低体液免疫和细胞介导的免疫。染料木黄酮对胸腺的这些作用是通过雌激素受体（ER）介导和非ER介导的途径发生的。注射染料木黄酮产生的影响最为显著，但给小鼠喂食后使其血清染料木黄酮浓度与食用大豆配方奶粉的人类婴儿所报道的浓度相似也有明显效果。对雌二醇和染料木黄酮对新生胸腺影响的微阵列分析表明，雌二醇影响参与转录、凋亡、细胞周期以及胸腺发育和功能的基因；染料木黄酮对许多雌二醇靶基因有类似影响，但也有雌二醇未重复的独特作用。尽管有大量研究表明染料木黄酮对免疫有抑制作用，但其他啮齿动物研究报告称染料木黄酮或其他植物雌激素可刺激免疫功能的各个方面。尽管目前的数据强烈表明染料木黄酮可能在生理浓度下调节免疫功能，但仍需要进一步研究来明确确定染料木黄酮和大豆对胸腺和免疫的总体影响，其可能因年龄、物种和特定终点而有所不同。
