Impact of androgenic/antiandrogenic compounds (AAC) on human sex steroid metabolizing key enzymes.
Various pesticides, industrial pollutants and synthetic compounds, to which human populations are exposed, are known or suspected to interfere with endogenous sex hormone functions. Such interference potentially affect the development and expression of the male and female reproductive system or both. Chemicals in this class are thus referred to as endocrine disruptors (ED). This emphazises on the relevance of screening ED for a wide range of sex hormone-mimicking effects. These compounds are believed to exert influence on hormonal actions predominantly by (i) interfering with endogenous steroids in that they functionally interact with plasma membrane-located receptors as well as with nuclear receptors both for estrogens and androgens or (ii) affecting the levels of sex hormones as a result of their impact on steroid metabolizing key enzymes. Essential sex hormone-related enzymes within the endocrine system of humans are aromatase, 5alpha-reductase 2 as well as specific sulfotransferases and sulfatases (so-called phase I and phase II enzymes, respectively). Using suitable human tissues and human cancer cell lines (placenta, prostate, liver and JEG-3, lymph node carcinoma of prostate (LnCaP) cells) we investigated the impact of 10 widely used chemicals suspected of acting as ED with androgenic or antiandrogenic activity (so-called AAC) on the activity of these sex hormone metabolizing key enzymes in humans. In addition, the respective effects of six substances were also studied as positive controls due to their well-known specific hormonal agonistic/antagonistic activities. The aim of this report and subsequent investigations is to improve human health risk assessment for AAC and other ED.
Alléra
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Department of Clinical Biochemistry, University of Bonn, 53105 Bonn, Germany. allera@uni-bonn.de
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King
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Steglich
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Klingmüller
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D000726:Androgen Antagonists / Q000633:toxicity*; D000728:Androgens / Q000633:toxicity*; D002478:Cells, Cultured; D004702:Endocrine Glands / Q000187:drug effects*; D012739:Gonadal Steroid Hormones / Q000378:metabolism*; D006801:Humans; D015262:Xenobiotics / Q000633:toxicity*
D000726:Androgen Antagonists; D000728:Androgens; D012739:Gonadal Steroid Hormones; D015262:Xenobiotics