Déchaud H, Ravard C, Claustrat F, de la Perrière A B, Pugeat M
Hospices Civils de Lyon, Laboratoire Central de Biochimie, France.
Steroids. 1999 May;64(5):328-34. doi: 10.1016/s0039-128x(98)00114-7.
This study reports on some environmental chemicals with estrogenic activity (xenoestrogens) and their binding interaction for human plasma sex-hormone binding globulin (hSHBG). The binding affinity constant of these xenoestrogens was measured in equilibrium conditions by solid phase binding assay, and their ability to displace endogenous testosterone and estradiol from hSHBG binding sites was determined with an ammonium sulfate precipitation assay in native plasma from normal men and women. The data showed that some of these xenoestrogens bind hSHBG, with a reversible and competitive binding activity for both [3H]testosterone and [3H]17beta-estradiol and with no apparent decrease in the number of hSHBG binding sites. Their respective binding affinity constants were low, ranging from 0.02 to 7.8 10(5) 1 x mol(-1). However, in native plasma from normal men and women, they were able to dose-dependently increase concentrations of hSHBG-unbound testosterone and/or estradiol. In this study, 4-nonylphenol and 4-tertoctylphenol, two alkylphenols used as surfactants in many commercial products, and bisphenol A and O-hydroxybiphenyl, widely used in the plastics industry, were identified as potent hSHBG-ligands. Additionally, the flavonoid phytoestrogens genistein and naringenin were also identified as hSHBG ligands, whereas their glucoside derivatives, genistin and naringin, had no binding activity for hSHBG. From these data, it is suggested that hSHBG binding may transport some contaminant xenoestrogens into the plasma and modulate their bioavailability to cell tissues. On the other hand, xenoestrogens may also displace endogenous sex steroid hormones from hSHBG binding sites and disrupt the androgen-to-estrogen balance. Whether xenoestrogen SHBG ligands could reach high enough concentrations in the blood to expose humans to any such effect merits further investigation.
本研究报告了一些具有雌激素活性的环境化学物质（外源性雌激素）及其与人血浆性激素结合球蛋白（hSHBG）的结合相互作用。通过固相结合试验在平衡条件下测定这些外源性雌激素的结合亲和力常数，并采用硫酸铵沉淀试验在正常男性和女性的天然血浆中测定它们从hSHBG结合位点置换内源性睾酮和雌二醇的能力。数据表明，其中一些外源性雌激素与hSHBG结合，对[3H]睾酮和[3H]17β-雌二醇均具有可逆的竞争性结合活性，且hSHBG结合位点数量无明显减少。它们各自的结合亲和力常数较低，范围为0.02至7.8×10⁵ 1×mol⁻¹。然而，在正常男性和女性的天然血浆中，它们能够剂量依赖性地增加未与hSHBG结合的睾酮和/或雌二醇的浓度。在本研究中，4-壬基酚和4-叔辛基酚这两种在许多商业产品中用作表面活性剂的烷基酚，以及在塑料工业中广泛使用的双酚A和邻羟基联苯，被确定为强效的hSHBG配体。此外，类黄酮植物雌激素染料木黄酮和柚皮素也被确定为hSHBG配体，而它们的葡萄糖苷衍生物染料木苷和柚皮苷对hSHBG没有结合活性。根据这些数据，提示hSHBG结合可能将一些外源性污染物雌激素转运到血浆中，并调节它们对细胞组织的生物利用度。另一方面，外源性雌激素也可能从hSHBG结合位点置换内源性性激素，破坏雄激素与雌激素的平衡。外源性雌激素SHBG配体在血液中是否能够达到足够高的浓度以使人类受到任何此类影响，值得进一步研究。
