In utero exposure to the antiandrogen di-(2-ethylhexyl) phthalate decreases adrenal aldosterone production in the adult rat.
In utero exposure to the antiandrogen di-(2-ethylhexyl) phthalate decreases adrenal aldosterone production in the adult rat.
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在子宫内暴露于抗雄激素邻苯二甲酸二(2-乙基己基)酯会降低成年大鼠肾上腺醛固酮的产生。
DOI：
10.1095/biolreprod.110.089920
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发表时间：
2011
影响因子：
3.6
通讯作者：
Papadopoulos,Vassilios
中科院分区：
文献类型：
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作者：
Martinez-Arguelles,DanielB;Guichard,Theodore;Culty,Martine;Zirkin,BarryR;Papadopoulos,Vassilios
我们以前报道过，在子宫内暴露于增塑剂邻苯二甲酸二（2-乙基己基）酯（DEHP）的男性胎儿，导致在成人睾丸激素的循环水平下降，而不影响睾丸间质细胞数量，促黄体激素水平，或类固醇生成酶的表达。胎儿暴露于DEHP导致成年Leydig细胞中盐皮质激素受体（MR; NR 3C 2）表达降低。在目前的研究中，从妊娠第14天到出生，用20、50、100、300或750 mg kg− 1天− 1的DEHP处理妊娠Sprague-Dawley母鼠，导致出生后第60天（PND 60）血清醛固酮水平显著降低，但在PND 21天血清皮质酮水平没有显著降低。对钾、血管紧张素II或促肾上腺皮质激素（ACTH）的循环水平无影响。然而，AT受体Agtr 1a、Agtr 1b和Agtr 2 mRNA的表达减少。与醛固酮生物合成有关的蛋白质和酶的mRNA水平不受子宫内DEHP处理的影响，但Cyp 11b 2除外，其在高剂量（≥500 mg kg− 1天−1）下降低。本文提供的数据以及我们之前观察到的醛固酮通过MR介导的机制刺激睾酮产生，表明子宫内暴露于DEHP会导致肾上腺醛固酮合成和Leydig细胞MR表达减少，从而导致睾酮产生减少。成人。此外，这些结果表明存在DEHP敏感的肾上腺-睾丸轴调节雄激素的形成。
We previously reported that in utero exposure of the male fetus to the plasticizer di-(2-ethylhexyl) phthalate (DEHP) resulted in decreased circulating levels of testosterone in the adult without affecting Leydig cell numbers, luteinizing hormone levels, or steroidogenic enzyme expression. Fetal exposure to DEHP resulted in reduced mineralocorticoid receptor (MR; NR3C2) expression in adult Leydig cells. In the present studies, treatment of pregnant Sprague-Dawley dams from Gestational Day 14 until birth with 20, 50, 100, 300, or 750 mg kg−1day−1of DEHP resulted in significant sex-specific decreases in serum aldosterone but not corticosterone levels at Postnatal Day 60 (PND60) but not at PND21. There was no effect on circulating levels of potassium, angiotensin II or adrenocorticotropin hormone (ACTH). However, there was reduced expression of AT receptorAgtr1a,Agtr1b, andAgtr2mRNAs. The mRNA levels of proteins and enzymes implicated in aldosterone biosynthesis were not affected by in utero DEHP treatment except forCyp11b2, which was decreased at high (≥500 mg kg−1day−1) doses. The data presented herein, together with our previous observation that aldosterone stimulates testosterone production via an MR-mediated mechanism, suggest that in utero exposure to DEHP causes reduction in both adrenal aldosterone synthesis and MR expression in Leydig cells, leading to reduced testosterone production in the adult. Moreover, these results suggest the existence of a DEHP-sensitive adrenal-testis axis regulating androgen formation.