Several environmental oestrogens are also anti-androgens.
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.
Sohoni
P
P
Department of Biology and Biochemistry, Brunel University, Uxbridge, Middlesex, UK.
Sumpter
J P
JP
D000726:Androgen Antagonists / Q000494:pharmacology*; D000728:Androgens / Q000494:pharmacology*; D001559:Benzhydryl Compounds; D001681:Biological Assay; D003634:DDT; D003633:Dichlorodiphenyl Dichloroethylene / Q000494:pharmacology; D004054:Diethylstilbestrol / Q000494:pharmacology; D004787:Environmental Pollution; D004965:Estrogen Antagonists / Q000494:pharmacology*; D004967:Estrogens / Q000494:pharmacology*; D005485:Flutamide / Q000494:pharmacology; D005659:Fungicides, Industrial / Q000494:pharmacology; D015870:Gene Expression; D006728:Hormones / Q000494:pharmacology*; D006801:Humans; D010080:Oxazoles / Q000494:pharmacology; D010575:Pesticides / Q000494:pharmacology; D010636:Phenols / Q000494:pharmacology; D011944:Receptors, Androgen / Q000187:drug effects / Q000235:genetics; D011960:Receptors, Estrogen / Q000187:drug effects / Q000235:genetics; D012441:Saccharomyces cerevisiae / Q000235:genetics; D015262:Xenobiotics / Q000494:pharmacology; D000098826:Bisphenol A Compounds
D000726:Androgen Antagonists; D000728:Androgens; D001559:Benzhydryl Compounds; D003634:DDT; D003633:Dichlorodiphenyl Dichloroethylene; D004054:Diethylstilbestrol; D004965:Estrogen Antagonists; D004967:Estrogens; D005485:Flutamide; D005659:Fungicides, Industrial; D006728:Hormones; D010080:Oxazoles; D010575:Pesticides; D010636:Phenols; D011944:Receptors, Androgen; D011960:Receptors, Estrogen; D015262:Xenobiotics; C041594:4-nonylphenol; C025643:vinclozolin; C006780:bisphenol A; D000098826:Bisphenol A Compounds