Eil C, Nisula B C
Department of Medicine, Roger Williams General Hospital, Brown University, Providence, RI 02908.
J Steroid Biochem. 1990 Mar;35(3-4):409-14. doi: 10.1016/0022-4731(90)90248-q.
The pyrethroids are a class of natural and synthetic pesticides which were associated with an epidemic of gynecomastia in Haitian men in 1981. In the present study we tested several pyrethroids for their ability to interact with androgen binding sites in dispersed, intact human genital skin fibroblasts and in human plasma to sex hormone binding globulin (SHBG). All the pyrethroids tested inhibited fibroblast binding of [3H]methyltrienolone (R1881) at 22 degrees C with the following rank order of potency:pyrethrins greater than bioallethrin greater than fenvalerate greater than fenothrin greater than fluvalinate greater than permethrin greater than resmethrin. 50% displacement of [3H]R1881 binding to fibroblast androgen receptors was achieved by 1.5-44 x 10(-5) M concentrations of the competitors, respectively. Previous studies with cimetidine, a known inhibitor of androgen receptor binding, showed 50% competition at a concentration of 1.4 x 10(-4) M in this system. Scatchard analysis of binding experiments performed with increasing concentrations of [3H]R1881 in the presence of the pyrethroids indicated that the binding inhibition was competitive. On the other hand, of the pyrethroids examined only the pyrethrins (50% inhibition) and bioallethrin (43% inhibition) were able to displace [3H]testosterone from SHBG when tested at a concentration of 10(-4) M. These data indicate that a novel class of non-steroidal compounds, the pyrethroids, can interact competitively with human androgen receptors and SHBG. These findings provide a mechanism by which chronic exposure of humans or animals to pesticides containing these compounds may result in disturbances in endocrine effects relating to androgen action.
拟除虫菊酯是一类天然和合成的杀虫剂，1981年海地男性中曾出现与这类杀虫剂相关的男性乳房发育症流行。在本研究中，我们测试了几种拟除虫菊酯与分散的完整人类生殖器皮肤成纤维细胞以及人血浆中与性激素结合球蛋白（SHBG）的雄激素结合位点相互作用的能力。所有测试的拟除虫菊酯在22℃时均抑制[3H]甲基三烯醇酮（R1881）与成纤维细胞的结合，其效力顺序如下：除虫菊素＞生物丙烯菊酯＞氰戊菊酯＞苯醚菊酯＞氟胺氰菊酯＞氯菊酯＞苄呋菊酯。[3H]R1881与成纤维细胞雄激素受体结合被50%置换时，竞争者的浓度分别为1.5 - 44×10⁻⁵ M。先前对已知雄激素受体结合抑制剂西咪替丁的研究表明，在此系统中，浓度为1.4×10⁻⁴ M时可产生50%的竞争作用。在拟除虫菊酯存在的情况下，对用递增浓度的[3H]R1881进行的结合实验进行Scatchard分析表明，结合抑制是竞争性的。另一方面，在所检测的拟除虫菊酯中，仅除虫菊素（50%抑制）和生物丙烯菊酯（43%抑制）在10⁻⁴ M浓度下测试时能够从SHBG中置换出[3H]睾酮。这些数据表明，一类新型的非甾体化合物——拟除虫菊酯，能够与人雄激素受体和SHBG发生竞争性相互作用。这些发现提供了一种机制，通过该机制，人类或动物长期接触含有这些化合物的杀虫剂可能会导致与雄激素作用相关的内分泌效应紊乱。
