Inhibition of testicular steroidogenesis by the xenoestrogen bisphenol a is associated with reduced pituitary luteinizing hormone secretion and decreased steroidogenic enzyme gene expression in rat Leydig cells
Inhibition of testicular steroidogenesis by the xenoestrogen bisphenol a is associated with reduced pituitary luteinizing hormone secretion and decreased steroidogenic enzyme gene expression in rat Leydig cells
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DOI：
10.1210/en.2003-1174
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发表时间：
2004-02-01
期刊：
影响因子：
4.8
通讯作者：
Hardy, MP
中科院分区：
文献类型：
--
作者：
Akingbemi, BT;Sottas, CM;Hardy, MP
双酚A（BPA）是聚碳酸酯塑料中的一种单体，也是食品包装和牙科用树脂的一种成分，人类暴露于双酚A（BPA）中是很重要的。在本报告中，大鼠暴露于2.4 μ g/kg。D（接近环境中BPA水平的剂量）从出生后第21 - 35天抑制血清LH（0.21 +/- 0.05 ng/ml;与对照组相比，0.52 +/- 0.04; P < 0.01）和睾酮（T）水平（1.62 +/- 0.16 ng/ml; vs.对照组，2.52 +/- 0.21; P < 0.05），与通过RT-PCR测量的LH β降低和雌激素受体β垂体mRNA水平增加相关。用0.01 nM BPA处理成年Leydig细胞，由于类固醇生成酶17 α-羟化酶/17-20裂解酶的表达降低，T生物合成降低了25%。在暴露于2.4 μ g、10 μ g或100 mg/kg的大鼠中，BPA将血清17 β-雌二醇水平从0.31 +/- 0.02 ng/ ml（对照）降低至0.22 +/- 0.02、0.19 +/- 0.02和0.23 +/- 0.03 ng/ml。21 ~ 35日龄组间差异显著（P < 0.05），这是由于BPA能抑制睾丸间质细胞芳香化酶活性。妊娠期和哺乳期母鼠的暴露，即从妊娠第12天到出生后第21天，睾丸间质液中的T水平从420 +/- 34（对照）降低到成年期的261 +/- 22（P < 0.05）ng/ ml，这意味着围产期是暴露于BPA的敏感窗口。由于BPA已在几个人群中进行了测量，因此有必要进行进一步研究以评估BPA对男性生育力的影响。
Exposure of humans to bisphenol A (BPA), a monomer in polycarbonate plastics and a constituent of resins used in food packaging and dentistry, is significant. In this report exposure of rats to 2.4 mug/kg . d (a dose that approximates BPA levels in the environment) from postnatal d 21 - 35 suppressed serum LH (0.21 +/- 0.05 ng/ml; vs. control, 0.52 +/- 0.04; P < 0.01) and testosterone (T) levels (1.62 +/- 0.16 ng/ml; vs. control, 2.52 +/- 0.21; P < 0.05), in association with decreased LHbeta and increased estrogen receptor beta pituitary mRNA levels as measured by RT-PCR. Treatment of adult Leydig cells with 0.01 nM BPA decreased T biosynthesis by 25% as a result of decreased expression of the steroidogenic enzyme 17alpha-hydroxylase/17-20 lyase. BPA decreased serum 17beta-estradiol levels from 0.31 +/- 0.02 ng/ ml (control) to 0.22 +/- 0.02, 0.19 +/- 0.02, and 0.23 +/- 0.03 ng/ml in rats exposed to 2.4 mug, 10 mug, or 100 mg/kg . d BPA, respectively, from 21 - 35 d of age ( P < 0.05) due to its ability to inhibit Leydig cell aromatase activity. Exposures of pregnant and nursing dams, i.e. from gestation d 12 to postnatal d 21, decreased T levels in the testicular interstitial fluid from 420 +/- 34 ( control) to 261 +/- 22 ( P < 0.05) ng/ ml in adulthood, implying that the perinatal period is a sensitive window of exposure to BPA. As BPA has been measured in several human populations, further studies are warranted to assess the effects of BPA on male fertility.