Persistent DDT metabolite p,p'–DDE is a potent androgen receptor antagonist

  title={Persistent DDT metabolite p,p'–DDE is a potent androgen receptor antagonist},
  author={William R. Kelce and Christy R. Stone and Susan C. Laws and Leon Earl Gray and Jon A. Kemppainen and Elizabeth M. Wilson},
THE increase in the number of reports of abnormalities in male sex development in wildlife and humans coincided with the introduction of 'oestrogenic' chemicals such as DDT (1,1,1-trichloro-2,2-bis(p-chlorophenyl)ethane) into the environment. Although these phenotypic alterations are thought to be mediated by the oestrogen receptor, they are also consistent with inhibition of androgen receptor-mediated events. Here we report that the major and persistent DDT metabolite,P,P′-DDE (l,l-dichloro-2… 

Environmental antiandrogens: developmental effects, molecular mechanisms, and clinical implications

In light of increasing concern over the potential endocrine disrupting effects of environmental pollutants, an in vitro/in vivo investigational strategy is presented which has proved useful in identifying chemicals with antiandrogen activity and their mechanism of action.

Inhibition of androgen receptor-dependent transcriptional activity by DDT isomers and methoxychlor in HepG2 human hepatoma cells.

The results demonstrate that the HepG2 assay is a sensitive and specific method for detecting chemical interaction with the androgen receptor, and should be useful for determining the role of multiple steroid receptors in the mechanism of action of endocrine active chemicals.

Alterations in male reproductive hormones in relation to environmental DDT exposure.

Interaction of Methoxychlor and Related Compounds with Estrogen Receptor α and β, and Androgen Receptor: Structure-Activity Studies

Some of the structural requirements for ERα and ERβ activity are identified and the complexity involved in determining the mechanism of action of endocrine-active chemicals that simultaneously act as agonists or antagonists through one or more hormone receptors is demonstrated.

Adverse effects of environmental antiandrogens and androgens on reproductive development in mammals.

Information is presented on the classes of environmental chemicals that display antiandrogenic and androgenic activities in vitro and in vivo and an insight into how exposure to mixtures these chemicals might behave in utero is provided.



Estrogenic activities of chlorinated hydrocarbons.

Some DDT analogs are estrogenic, particularly o,p'-DDT, which comprises approximately 15-20% of the commercial DDT mixture, and it is probable that phenolic metabolites are responsible for its estrogenic activity.

Environmental hormone disruptors: evidence that vinclozolin developmental toxicity is mediated by antiandrogenic metabolites.

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Developmental effects of an environmental antiandrogen: the fungicide vinclozolin alters sex differentiation of the male rat.

The observation of perinatal-induced agenesis of the prostate and blocked testicular descent, a pattern of malformations nearly identical to that reported for the antiandrogen flutamide, is consistent with other recent evidence that this fungicide is an androgen-receptor antagonist.

DDT homologues: estrogen-like effects on the vagina, uterus and pituitary of the rat.

It is demonstrated that o,p′-DDT and one of its major metabolites, DDA, exert estrogenic activity by stimulating uterine and vaginal tissue and reduce serum LH, pr...

Estrogenic action of DDT and its analogs.

Treatment with antiandrogens induces an androgen‐repressed gene in the rat ventral prostate

The results suggest that while neither cyproterone acetate nor flutamide fully repress the androgen‐dependent functions of the prostate, they do induce some of the androgens‐repressed sequences in the prostate that have been implicated in the process of cell death.

Comparison of the effects of the 5 alpha-reductase inhibitor finasteride and the antiandrogen flutamide on prostate and genital differentiation: dose-response studies.

Results suggest that testosterone (T) can compensate for DHT to some degree at the level of the androgen receptor, despite increasingly higher doses of the antiandrogen flutamide.

Absorption, storage, and metabolic conversion of ingested DDT and DDT metabolites in man.

Serum and adipose concentrations of DDT and DDT metabolites in response to these dosings have indicated that the initial dechlorinated DDT is of critical importance to its metabolic fate, and conversion to the saturated p,p′-DDD makes possible further degradation to the readily excreted p, p′-DDA.