Sohoni P, Sumpter J P
Department of Biology and Biochemistry, Brunel University, Uxbridge, Middlesex, UK.
J Endocrinol. 1998 Sep;158(3):327-39. doi: 10.1677/joe.0.1580327.
There is presently considerable interest in endocrine disruption which is a new area of endocrinology concerned with chemicals that mimic hormones, in particular sex steroids. It has been hypothesised that exposure to such chemicals may be responsible for adverse effects in both humans and wildlife. Until now, chemicals that mimic oestrogens (so-called xenoestrogens) have been the main focus of endocrine disruption research. However, recent evidence suggests that many abnormalities in the male reproductive system may be mediated via the androgen receptor. By blocking androgen action, exposure to an anti-androgen may cause changes similar to those associated with oestrogen exposure. We have used in vitro yeast-based assays to detect oestrogenic, anti-oestrogenic, androgenic and anti-androgenic activities in a variety of chemicals of current interest. We show that many of the so-called 'environmental oestrogens' also possess anti-androgenic activity. The previously reported anti-androgenic activities of vinclozolin and p,p'-1,1-dichloro-2,2-bis(p-chlorophenyl) ethylene (DDE) were confirmed. We also found that o,p'-1,1,1,-trichloro-2,2-bis(p-chlorophenyl)ethane (DDT), bisphenol A and butyl benzyl phthalate were anti-androgenic. However, not all xenoestrogens are also anti-androgenic, because nonylphenol was found to be a weak androgen agonist. Our results demonstrate that hormone-mimicking chemicals can have multiple hormonal activities, which may make it difficult to interpret their mechanisms of action in vivo. Although not a specific objective of this study, our results also demonstrate that yeast-based assays are powerful tools with which to investigate both agonist and antagonistic hormonal activities of chemicals.
目前,内分泌干扰备受关注,它是内分泌学的一个新领域,涉及模拟激素的化学物质,尤其是性类固醇。据推测,接触此类化学物质可能会对人类和野生动物产生不良影响。到目前为止,模拟雌激素的化学物质(所谓的外源性雌激素)一直是内分泌干扰研究的主要焦点。然而,最近的证据表明,男性生殖系统中的许多异常可能是通过雄激素受体介导的。通过阻断雄激素作用,接触抗雄激素可能会导致与雌激素接触相关的类似变化。我们使用基于酵母的体外试验来检测各种当前感兴趣的化学物质中的雌激素活性、抗雌激素活性、雄激素活性和抗雄激素活性。我们发现,许多所谓的“环境雌激素”也具有抗雄激素活性。先前报道的乙烯菌核利和p,p'-1,1-二氯-2,2-双(对氯苯基)乙烯(DDE)的抗雄激素活性得到了证实。我们还发现,o,p'-1,1,1-三氯-2,2-双(对氯苯基)乙烷(DDT)、双酚A和邻苯二甲酸丁苄酯具有抗雄激素活性。然而,并非所有外源性雌激素都具有抗雄激素活性,因为壬基酚被发现是一种弱雄激素激动剂。我们的结果表明,模拟激素的化学物质可以具有多种激素活性,这可能使其体内作用机制难以解释。虽然这不是本研究的具体目标,但我们的结果也表明,基于酵母的试验是研究化学物质激动剂和拮抗激素活性的有力工具。