Environmental Xenobiotics May Disrupt Normal Endocrine Function by Interfering with the Binding of Physiological Ligands to Steroid Receptors and Binding Proteins

• Published in: Environmental health perspectives 1997-03, Vol.105 (3), p.294-301
• Main Author: Danzo, Benjamin J.
• Format: Article
• Language: English
• Subjects: Androgen receptors; Androgen-Binding Protein - drug effects; Androgen-Binding Protein - metabolism; Animals; Binding, Competitive; Carrier proteins; Cells, Cultured; Charcoal; Cytosol; Estrogen receptors; Female; Humans; Ligands; Male; Prostate; Rabbits; Rats; Rats, Sprague-Dawley; Receptors; Receptors, Androgen - drug effects; Receptors, Androgen - metabolism; Receptors, Estradiol - drug effects; Receptors, Estradiol - metabolism; Sex Hormone-Binding Globulin - drug effects; Sex Hormone-Binding Globulin - metabolism; Steroids; Xenobiotics; Xenobiotics - toxicity
• ISSN: 0091-6765; 1552-9924
• DOI: 10.1289/ehp.97105294

The disruption of the reproductive system of male and female animals in the wild has been attributed to environmental chemicals (xenobiotics). The effects seen mirror alterations one might anticipate if the steroid hormone-dependent processes that regulate these systems were impaired. To determine whether xenobiotics (present at a concentration of 100 μM) exert their action through steroid-mediated pathways, we examined their ability to inhibit the binding of [3 H]physiological ligands (present at a concentration of 7 nM) to the androgen and estrogen receptors, rat androgen-binding protein (ABP), and human sex hormone-binding globulin (hSHBG). The γ- and δ-isomers of hexachlorocyclohexane, congeners of dichlorodiphenyl-trichloroethane (DDT; p,p′-DDT; p,p′-DDE; o,p′-DDT), dieldrin, atrazine, and pentachlorophenol, caused a statistically significant inhibition of specific binding of [3 H]5α - DHT to the androgen receptor that ranged from 100% (p,p′-DDE) to 25% (dieldrin). Methoxychlor, o,p′-DDT, pentachlorophenol, and nonylphenol significantly reduced [3 H]17β -estradiol binding to the estrogen receptor by 10, 60, 20, and 75%, respectively. The binding of [3 H]5α - DHT to ABP was inhibited 70% by the δ-isomer of hexachlorocyclohexane, but the γ-isomer did not reduce binding significantly. Methoxychlor, p,p′-DDT, atrazine, and nonylphenol reduced [3 H]5α - DHT binding to ABP by approximately 40%. Nonylphenol reduced the binding of [3 H]5α - DHT to hSHBG by 70%. Hexachlorocyclohexane reduced [3 H]5α - DHT binding to hSHBG by 20%, but the stereospecific effects observed with ABP did not occur. o,p′-DDT and pentachlorophenol resulted in a statistically significant 20% inhibition of [3 H]5α - DHT binding to hSHBG. Some xenobiotics resulted in dissociation of [3 H]ligands from their binding proteins that was statistically identical to that caused by the unlabeled natural ligand, whereas others resulted in slower or more rapid dissociation rates.