Penza Marialetizia, Montani Claudia, Romani Annalisa, Vignolini Pamela, Ciana Paolo, Maggi Adriana, Pampaloni Barbara, Caimi Luigi, Di Lorenzo Diego
3rd Laboratory/Biotechnology, Civic Hospital of Brescia, Brescia, Italy.
Toxicol Sci. 2007 Jun;97(2):299-307. doi: 10.1093/toxsci/kfm036. Epub 2007 Mar 3.
Isoflavones are important dietary compounds that are consumed with the daily diet and elicit important biological actions. Here we report on the ability of genistein to partially accumulate in body depots of male mice, be released following fasting, and modulate the actions of estradiol and environmental estrogens in reproductive and nonreproductive target organs of estrogen-reporter mice (ERE-tK-luciferase). After the consumption of 50 mg/kg/day for 3 days, genistein accumulates in body compartments where it remains at functionally active levels for at least 15 days. Following 48 h of fasting, its concentration increased in serum from 99 +/- 13 to 163 +/- 17 nM. These levels are sufficient to exert an estrogenic effect in the testis and liver, as revealed by a twofold increase in luciferase gene expression. beta-Benzene-hexachloride (betaBHC) given at the concentration of 100 mg/kg/day for 3 days also accumulates in the body and is released by fasting, reaching serum levels of 176 +/- 33 nM, upregulating the luciferase gene in the liver and inhibiting its expression in the testis. When genistein was given in combination with betaBHC at doses sufficient to induce accumulation of both in body depots, the genistein mobilized by fasting reversed the action of the mobilized betaBHC in the testis. Acute administration of nutritional doses of genistein inhibited the action of estradiol and reversed the antiestrogenic action of o,p'-DDT: 1,1,1,-trichloro-2(p-chlorophenyl)-2-(o-chlorophenyl)ethane in the liver and the antiestrogenic action of betaBHC in the testis. Genistein had an additive effect with the ER agonist p,p'-DDT: 1,1,1,-trichloro-2,2-bis(p-chlorophenyl)ethane in the liver. The observed effects may be relevant to a protective action of phytoestrogens against estrogen receptor-interacting pollutants as well as the dietary modulation of estradiol action.
异黄酮是日常饮食中摄入的重要膳食化合物，具有重要的生物学作用。在此，我们报告了染料木黄酮在雄性小鼠体内储存部位部分蓄积的能力，禁食后其被释放，并在雌激素报告基因小鼠（ERE - tK - 荧光素酶）的生殖和非生殖靶器官中调节雌二醇和环境雌激素的作用。在以50毫克/千克/天的剂量摄入3天后，染料木黄酮在体内各部位蓄积，并在至少15天内保持在功能活跃水平。禁食48小时后，其血清浓度从99±13纳摩尔/升增加到163±17纳摩尔/升。这些水平足以在睾丸和肝脏中发挥雌激素作用，荧光素酶基因表达增加了两倍就表明了这一点。以100毫克/千克/天的浓度给予β - 苯六氯（βBHC）3天，其也会在体内蓄积并通过禁食释放，血清水平达到176±33纳摩尔/升，上调肝脏中的荧光素酶基因并抑制其在睾丸中的表达。当以足以诱导两者在体内储存部位蓄积的剂量将染料木黄酮与βBHC联合给予时，禁食动员的染料木黄酮可逆转动员的βBHC在睾丸中的作用。急性给予营养剂量的染料木黄酮可抑制雌二醇的作用，并逆转o,p'-滴滴涕：1,1,1 - 三氯 - （对氯苯基） - （邻氯苯基）乙烷在肝脏中的抗雌激素作用以及βBHC在睾丸中的抗雌激素作用。染料木黄酮与雌激素受体激动剂p,p'-滴滴涕：1,1,1 - 三氯 - 2,2 - 双（对氯苯基）乙烷在肝脏中具有相加作用。观察到的这些效应可能与植物雌激素对雌激素受体相互作用污染物的保护作用以及雌二醇作用的饮食调节有关。
