Lema Sean C, Dickey Jon T, Schultz Irvin R, Swanson Penny
Physiology Program, Northwest Fisheries Science Center, National Oceanic and Atmospheric Administration, Seattle, Washington, USA.
Environ Health Perspect. 2008 Dec;116(12):1694-9. doi: 10.1289/ehp.11570. Epub 2008 Aug 1.
Polybrominated diphenyl ether (PBDE) flame retardants have been implicated as disruptors of the hypothalamic-pituitary-thyroid axis. Animals exposed to PBDEs may show reduced plasma thyroid hormone (TH), but it is not known whether PBDEs impact TH-regulated pathways in target tissues.
We examined the effects of dietary exposure to 2,2',4,4'-tetrabromodiphenyl ether (PBDE-47)-commonly the highest concentrated PBDE in human tissues-on plasma TH levels and on gene transcripts for glycoprotein hormone alpha-subunit (GPHalpha) and thyrotropin beta-subunit (TSHbeta) in the pituitary gland, the auto-induced TH receptors alpha and beta in the brain and liver, and the TH-responsive transcription factor basic transcription element-binding protein (BTEB) in the brain.
Breeding pairs of adult fathead minnows (Pimephales promelas) were given dietary PBDE-47 at two doses (2.4 microg/pair/day or 12.3 microg/pair/day) for 21 days.
Minnows exposed to PBDE-47 had depressed plasma thyroxine (T(4)), but not 3,5,3'-triiodothyronine (T(3)). This decline in T(4) was accompanied by elevated mRNA levels for TStHbeta (low dose only) in the pituitary. PBDE-47 intake elevated transcript for TH receptor alpha in the brain of females and decreased mRNA for TH receptor beta in the brain of both sexes, without altering these transcripts in the liver. In males, PBDE-47 exposure also reduced brain transcripts for BTEB.
Our results indicate that dietary exposure to PBDE-47 alters TH signaling at multiple levels of the hypothalamic-pituitary-thyroid axis and provide evidence that TH-responsive pathways in the brain may be particularly sensitive to disruption by PBDE flame retardants.
多溴二苯醚（PBDE）类阻燃剂被认为是下丘脑 - 垂体 - 甲状腺轴的干扰物。暴露于多溴二苯醚的动物可能会出现血浆甲状腺激素（TH）水平降低，但尚不清楚多溴二苯醚是否会影响靶组织中甲状腺激素调节的途径。
我们研究了饮食中暴露于2,2',4,4'-四溴二苯醚（PBDE - 47）（通常是人体组织中浓度最高的多溴二苯醚）对血浆甲状腺激素水平以及垂体中糖蛋白激素α亚基（GPHα）和促甲状腺激素β亚基（TSHβ）、大脑和肝脏中自身诱导的甲状腺激素受体α和β以及大脑中甲状腺激素反应性转录因子基本转录元件结合蛋白（BTEB）的基因转录本的影响。
成年黑头呆鱼（Pimephales promelas）亲鱼以两种剂量（2.4微克/对/天或12.3微克/对/天）给予饮食中的PBDE - 47，持续21天。
暴露于PBDE - 47的呆鱼血浆甲状腺素（T4）降低，但3,5,3'-三碘甲状腺原氨酸（T3）未降低。T4的这种下降伴随着垂体中TSHβ的mRNA水平升高（仅低剂量时）。PBDE - 47的摄入使雌性大脑中甲状腺激素受体α的转录本升高，使两性大脑中甲状腺激素受体β的mRNA降低，而肝脏中的这些转录本未改变。在雄性中，PBDE - 47暴露还降低了大脑中BTEB的转录本。
我们的结果表明，饮食中暴露于PBDE - 47会在下丘脑 - 垂体 - 甲状腺轴的多个水平改变甲状腺激素信号传导，并提供证据表明大脑中的甲状腺激素反应途径可能对多溴二苯醚阻燃剂的干扰特别敏感。
