Kim Hee-Su, Kim Yong-Bin, Choi Donchan, Cheon Yong-Pil, Lee Sung-Ho
Dept. of Biotechnology, Sangmyung University, Seoul 03016, Korea.
Dept. of Life Science, Yong-In University, Yongin 17092, Korea.
Dev Reprod. 2017 Dec;21(4):441-448. doi: 10.12717/DR.2017.21.4.441. Epub 2017 Dec 31.
Bisphenol-A(BPA) is a member of alkylphenol family, and shows adverse effects including reduced fertility, reproductive tract abnormalities, metabolic disorder, cancer induction, neurotoxicity and immunotoxicity. In the present study, we conducted Hershberger assay to evaluate whether the two candidates to replace BPA have androgenic or antiandrogenic activity. The assay was carried out using immature castrated Sprague-Dawley male rats. After 7 days of the surgery, testosterone propionate (TP, 0.4 mg/kg/day) and test materials (low dose, 40 mg/kg/day; high dose, 400 mg/kg/day) were administered for 10 consecutive days by subcutaneous (s.c.) injection and oral gavage, respectively. Test materials were BPA, isosorbide (ISO) and cyclohexanedimethanol (CHDM). The rats were necropsied, and then the weights of five androgen-dependent tissues [ventral prostate, seminal vesicle, levator ani-bulbocavernosus (LABC) muscle, paired Cowper's glands, and glans penis] and three androgen-insensitive tissues (kidney, spleen and liver) were measured. All test materials including BPA did not exhibit any androgenic activity in the assay. On the contrary, antiandrogen-like activities were found in all test groups, and the order of the intensity was CHDM > BPA > ISO in the five androgen-sensitive tissues. There was no statistical difference between low dose treatment and high dose treatment of BPA group as well as ISO group. In CHDM group, high dose treatment exhibited most severe weight reduction in all measured tissues. There was no statistical difference in androgen-insensitive tissue measurements, except BPA groups. Since the effects of ISO treatment on the accessory sex organs were much less or not present at all when compared to those of BPA, ISO could be a strong candidate to replace BPA. CHDM treatment brought most severe weight reduction in all of androgen-sensitive tissues, so this material should be excluded for further screening of BPA substitute selection.
双酚A（BPA）是烷基酚家族的一员，具有多种不良影响，包括生育能力下降、生殖道异常、代谢紊乱、致癌、神经毒性和免疫毒性。在本研究中，我们进行了赫什伯格试验，以评估两种替代双酚A的候选物是否具有雄激素活性或抗雄激素活性。该试验使用未成熟去势的斯普拉格-道利雄性大鼠进行。手术后7天，分别通过皮下注射和灌胃连续10天给予丙酸睾酮（TP，0.4mg/kg/天）和受试物（低剂量，40mg/kg/天；高剂量，400mg/kg/天）。受试物为双酚A、异山梨醇（ISO）和环己烷二甲醇（CHDM）。对大鼠进行尸检，然后测量五个雄激素依赖组织[腹侧前列腺、精囊、提肛肌-球海绵体肌（LABC）、成对的考珀氏腺和阴茎头]和三个雄激素不敏感组织（肾脏、脾脏和肝脏）的重量。包括双酚A在内的所有受试物在试验中均未表现出任何雄激素活性。相反，在所有试验组中均发现了抗雄激素样活性，在五个雄激素敏感组织中，强度顺序为CHDM>BPA>ISO。双酚A组和ISO组的低剂量处理和高剂量处理之间没有统计学差异。在CHDM组中，高剂量处理在所有测量组织中表现出最严重的体重减轻。除双酚A组外，雄激素不敏感组织测量无统计学差异。由于与双酚A相比，ISO处理对附属生殖器官的影响要小得多或根本不存在，因此ISO可能是替代双酚A的有力候选物。CHDM处理在所有雄激素敏感组织中导致最严重的体重减轻，因此该物质应排除在双酚A替代物选择的进一步筛选之外。
