Estrogen sensitivity of target genes and expression of nuclear receptor co-regulators in rat prostate after pre- and postnatal exposure to the ultraviolet filter 4-methylbenzylidene camphor.
Estrogen sensitivity of target genes and expression of nuclear receptor co-regulators in rat prostate after pre- and postnatal exposure to the ultraviolet filter 4-methylbenzylidene camphor.
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DOI：
10.1289/ehp.9134
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发表时间：
2007-12
影响因子：
10.4
通讯作者：
Lichtensteiger W
中科院分区：
文献类型：
--
作者：
Durrer S;Ehnes C;Fuetsch M;Maerkel K;Schlumpf M;Lichtensteiger W
在前期的研究中，我们发现紫外线过滤剂4-甲基苄叉樟脑（4-MBC）具有雌激素样活性，是一种优先的雌激素受体（ER）-β配体，对雌性大鼠生殖器官和两性大鼠脑发育有干扰作用。在这里，我们报告对男性发育的影响。4-在交配前、妊娠期和哺乳期，通过食物给予父母代MBC（0.7、7、24、47 mg/kg/天），并给予后代直至成年。通过实时逆转录聚合酶链反应测定前列腺叶中的mRNA，并通过Western印迹分析测定蛋白质。4-MBC延迟了男性青春期，降低了成年前列腺重量，并略微增加了睾丸重量。前列腺中雄激素受体（AR）、胰岛素样生长因子-1（IGF-1）、ER-α和ER-β的表达在mRNA和蛋白水平上发生改变，其中背外侧前列腺的作用强于腹侧前列腺。为了评估靶基因对雌激素的敏感性，在出生后第70天阉割后代，在出生后第84天注射17β-雌二醇（E2; 10或50 μg/kg，sc）或溶剂，并在6小时后处死。在腹侧前列腺中研究的E2对AR和IGF-1 mRNA的急性抑制通过4-MBC暴露减少。这伴随着腹侧和背外侧前列腺中共阻遏物N-CoR（核受体共阻遏物）蛋白的减少，而类固醇受体共激活因子-1（SRC-1）蛋白水平不受影响。我们的数据表明，4-MBC影响雄性生殖功能和器官的发育，观察到的最低不良影响水平为0.7 mg/kg。核受体辅助调节剂被揭示为内分泌干扰物的靶点，如前列腺中的N-CoR和子宫中的SRC-1所示。这可能对基因调控产生广泛影响。
In previous studies, we found that the ultraviolet filter 4-methyl-benzylidene camphor (4-MBC) exhibits estrogenic activity, is a preferential estrogen receptor (ER)-β ligand, and interferes with development of female reproductive organs and brain of both sexes in rats. Here, we report effects on male development. 4-MBC (0.7, 7, 24, 47 mg/kg/day) was administered in chow to the parent generation before mating, during gestation and lactation, and to offspring until adulthood. mRNA was determined in prostate lobes by real-time reverse transcription–polymerase chain reaction and protein was determined by Western blot analysis. 4-MBC delayed male puberty, decreased adult prostate weight, and slightly increased testis weight. Androgen receptor (AR), insulin-like growth factor-1 (IGF-1), ER-α, and ER-β expression in prostate were altered at mRNA and protein levels, with stronger effects in dorsolateral than ventral prostate. To assess sensitivity of target genes to estrogens, offspring were castrated on postnatal day 70, injected with 17β-estradiol (E2; 10 or 50 μg/kg, sc) or vehicle on postnatal day 84, and sacrificed 6 hr later. Acute repression of AR and IGF-1 mRNAs by E2, studied in ventral prostate, was reduced by 4-MBC exposure. This was accompanied by reduced co-repressor N-CoR (nuclear receptor co-repressor) protein in ventral and dorsolateral prostate, whereas steroid receptor coactivator-1 (SRC-1) protein levels were unaffected. Our data indicate that 4-MBC affects development of male reproductive functions and organs, with a lowest observed adverse effect level of 0.7 mg/kg. Nuclear receptor coregulators were revealed as targets for endocrine disruptors, as shown for N-CoR in prostate and SRC-1 in uterus. This may have widespread effects on gene regulation.
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影响因子：
4.5
作者：
Inui, M;Adachi, T;Miyatake, K
通讯作者：
Miyatake, K
影响因子：
4.8
作者：
Hodgson, MC;Astapova, I;Hollenberg, AN
通讯作者：
Hollenberg, AN
影响因子：
4.8
作者：
Lau, KM;Leav, I;Ho, SM
通讯作者：
Ho, SM
DOI：
10.1073/pnas.95.6.2920
发表时间：
1998-03-17
影响因子：
11.1
作者：
Lavinsky, RM;Jepsen, K;Rose, DW
通讯作者：
Rose, DW
影响因子：
4.1
作者：
Fritz, WA;Wang, J;Lamartiniere, CA
通讯作者：
Lamartiniere, CA