Sommer R J, Sojka K M, Pollenz R S, Cooke P S, Peterson R E
School of Pharmacy, University of Wisconsin, Madison, Wisconsin, 53706, USA.
Toxicol Appl Pharmacol. 1999 Mar 1;155(2):177-89. doi: 10.1006/taap.1998.8597.
Effects of stage of development and 2,3,7, 8-tetrachlorodibenzo-p-dioxin (TCDD) exposure on aryl hydrocarbon receptor (AhR) and AhR nuclear translocator (ARNT) protein concentrations in reproductive organs of male rats were determined. AhR protein levels in developing rat ventral and dorsolateral prostate decreased with age, declining approximately 70% between Postnatal Days (PND) 1 and 21. ARNT protein levels also decreased with age in dorsolateral, but not ventral prostate. The developmental decreases in prostatic AhR and ARNT protein were associated with decreases in AhR and ARNT mRNA. AhR and ARNT protein concentrations in fetal urogenital sinus on Gestation Days (GD) 16, 18, and 20 were similar to levels in ventral prostate on PND 7. TCDD exposure of adult male rats (0.2, 1, 5, or 25 micrograms/kg po, 24 h) decreased AhR but not ARNT protein in ventral and dorsolateral prostate, vas deferens, and epididymis. In utero and lactational TCDD exposure (1.0 micrograms/kg dam po, GD 15) did not alter ARNT levels but reduced prostatic AhR protein levels on PND 7 and delayed the developmental decrease in AhR protein in ventral and dorsolateral prostate. Finally, pretreatment of rat pups for 24 h with TCDD (5 micrograms/kg ip) down-regulated prostatic AhR protein on PND 7, but not on PND 1. Thus, prostatic AhR and ARNT protein and mRNA levels are regulated with age, whereas only AhR protein concentration is altered by TCDD exposure. Because in utero and lactational TCDD exposure only decreased prostatic AhR on PND 7, it is unlikely that down-regulation of AhR is the mechanism by which perinatal TCDD exposure impairs prostate development.
研究了发育阶段和2,3,7,8-四氯二苯并对二恶英(TCDD)暴露对雄性大鼠生殖器官中芳烃受体(AhR)和AhR核转运蛋白(ARNT)蛋白浓度的影响。发育中的大鼠腹侧和背外侧前列腺中的AhR蛋白水平随年龄下降,在出生后第1天(PND)和第21天之间下降了约70%。背外侧前列腺中的ARNT蛋白水平也随年龄下降,但腹侧前列腺中没有。前列腺AhR和ARNT蛋白的发育性下降与AhR和ARNT mRNA的下降相关。妊娠第16、18和20天胎儿泌尿生殖窦中的AhR和ARNT蛋白浓度与出生后第7天腹侧前列腺中的水平相似。成年雄性大鼠经TCDD暴露(0.2、1、5或25微克/千克,口服,24小时)后,腹侧和背外侧前列腺、输精管和附睾中的AhR蛋白减少,但ARNT蛋白未减少。子宫内和哺乳期TCDD暴露(1.0微克/千克,母鼠口服,妊娠第15天)并未改变ARNT水平,但降低了出生后第7天前列腺中的AhR蛋白水平,并延迟了腹侧和背外侧前列腺中AhR蛋白的发育性下降。最后,用TCDD(5微克/千克,腹腔注射)对幼鼠进行24小时预处理,降低了出生后第7天前列腺中的AhR蛋白,但未降低出生后第1天的水平。因此,前列腺AhR和ARNT蛋白及mRNA水平随年龄调节,而只有AhR蛋白浓度会因TCDD暴露而改变。由于子宫内和哺乳期TCDD暴露仅在出生后第7天降低了前列腺中的AhR,因此AhR的下调不太可能是围产期TCDD暴露损害前列腺发育的机制。