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.

[1]  J. Sumpter,et al.  Environmentally persistent alkylphenolic compounds are estrogenic. , 1994, Endocrinology.

[2]  R. Sharpe,et al.  Expression of cytochrome P450 17alpha-hydroxylase/C17-20 lyase in the fetal rat testis is reduced by maternal exposure to exogenous estrogens. , 1996, Endocrinology.

[3]  J. Sumpter,et al.  Estrogenic Effects of Effluents from Sewage Treatment Works , 1994 .

[4]  J. McLachlan,et al.  The anti-estrogenic activity of selected polynuclear aromatic hydrocarbons in yeast expressing human estrogen receptor. , 1996, Biochemical and biophysical research communications.

[5]  R. Bigsby,et al.  The environmental estrogen bisphenol A stimulates prolactin release in vitro and in vivo. , 1997, Endocrinology.

[6]  J. Sumpter,et al.  A variety of environmentally persistent chemicals, including some phthalate plasticizers, are weakly estrogenic. , 1995, Environmental health perspectives.

[7]  Edwin J. Routledge,et al.  Estrogenic activity of surfactants and some of their degradation products assessed using a recombinant yeast screen , 1996 .

[8]  B. Rattner,et al.  Avian endocrine responses to environmental pollutants. , 1984, The Journal of experimental zoology.

[9]  C. A. Harris,et al.  The estrogenic activity of phthalate esters in vitro. , 1997, Environmental health perspectives.

[10]  L. Gray,et al.  Persistent DDT metabolite p,p'–DDE is a potent androgen receptor antagonist , 1995, Nature.

[11]  R M Sharpe,et al.  Gestational and lactational exposure of rats to xenoestrogens results in reduced testicular size and sperm production. , 1995, Environmental health perspectives.

[12]  K. Korach,et al.  Alterations in estrogen levels during development affects the skeleton: use of an animal model. , 1995, Environmental health perspectives.

[13]  F. S. French,et al.  Binding properties of androgen receptors. Evidence for identical receptors in rat testis, epididymis, and prostate. , 1976, The Journal of biological chemistry.

[14]  T. Iguchi,et al.  Cellular effects of early exposure to sex hormones and antihormones. , 1992, International review of cytology.

[15]  A R Woodward,et al.  Developmental abnormalities of the gonad and abnormal sex hormone concentrations in juvenile alligators from contaminated and control lakes in Florida. , 1994, Environmental health perspectives.

[16]  N. Keiding,et al.  Do environmental estrogens contribute to the decline in male reproductive health? , 1995, Clinical chemistry.

[17]  N. Coldham,et al.  Evaluation of a recombinant yeast cell estrogen screening assay. , 1997, Environmental health perspectives.

[18]  J. Ashby,et al.  Activity of raloxifene in immature and ovariectomized rat uterotrophic assays. , 1997, Regulatory toxicology and pharmacology : RTP.

[19]  R. M. Sharpe,et al.  Are oestrogens involved in falling sperm counts and disorders of the male reproductive tract? , 1993, The Lancet.

[20]  A. Piersma,et al.  Evaluation of the OECD 421 reproductive toxicity screening test protocol using butyl benzyl phthalate. , 1995, Toxicology.

[21]  S. Safe Do environmental estrogens play a role in development of breast cancer in women and male reproductive problems , 1995 .

[22]  T. Colborn,et al.  Environmental estrogens: health implications for humans and wildlife. , 1995, Environmental health perspectives.

[23]  N Keiding,et al.  Evidence for decreasing quality of semen during past 50 years. , 1992, BMJ.

[24]  S. J. Harris,et al.  Estrogenic Activity of o, p'-DDT in the Mammalian Uterus and Avian Oviduct , 1968, Science.

[25]  C. Sonnenschein,et al.  p-Nonyl-phenol: an estrogenic xenobiotic released from "modified" polystyrene. , 1991, Environmental health perspectives.

[26]  L. Gray,et al.  Developmental effects of an environmental antiandrogen: the fungicide vinclozolin alters sex differentiation of the male rat. , 1994, Toxicology and applied pharmacology.

[27]  I. Purvis,et al.  An androgen-inducible expression system for Saccharomyces cerevisiae. , 1991, Gene.

[28]  L. Gray,et al.  Environmental hormone disruptors: evidence that vinclozolin developmental toxicity is mediated by antiandrogenic metabolites. , 1994, Toxicology and applied pharmacology.

[29]  J. McLachlan,et al.  Inhibition of progesterone receptor activity in yeast by synthetic chemicals. , 1996, Biochemical and biophysical research communications.

[30]  C Sonnenschein,et al.  The E-SCREEN assay as a tool to identify estrogens: an update on estrogenic environmental pollutants. , 1995, Environmental health perspectives.

[31]  K A Thayer,et al.  Relative binding affinity-serum modified access (RBA-SMA) assay predicts the relative in vivo bioactivity of the xenoestrogens bisphenol A and octylphenol. , 1997, Environmental health perspectives.

[32]  M D Shelby,et al.  Assessing environmental chemicals for estrogenicity using a combination of in vitro and in vivo assays. , 1996, Environmental health perspectives.

[33]  C. Portier,et al.  Evaluation of chemicals with endocrine modulating activity in a yeast-based steroid hormone receptor gene transcription assay. , 1997, Toxicology and applied pharmacology.

[34]  H BRICAIRE,et al.  Journal of Endocrinology , 1939, Nature.

[35]  J. Gustafsson,et al.  Cloning of a novel estrogen receptor expressed in rat prostate and ovary , 2022 .

[36]  D. Davis,et al.  Effects of pesticides on the ratio of 16 alpha/2-hydroxyestrone: a biologic marker of breast cancer risk. , 1995, Environmental health perspectives.

[37]  L. Guillette Endocrine disrupting environmental contaminants and developmental abnormalities in embryos , 1995 .

[38]  J. Gustafsson,et al.  Cloning of a novel receptor expressed in rat prostate and ovary. , 1996, Proceedings of the National Academy of Sciences of the United States of America.

[39]  D. Fry,et al.  DDT-induced feminization of gull embryos. , 1981, Science.

[40]  J. McLachlan,et al.  Differential interaction of natural and synthetic estrogens with extracellular binding proteins in a yeast estrogen screen , 1996, Steroids.