Endocrine-disrupting chemicals as modulators of sex steroid synthesis.
Endocrine-disrupting chemicals (EDCs) are typically identified as compounds that can interact with oestrogen or androgen receptors and thus act as agonists or antagonists of endogenous hormones. Growing evidence shows that they may also modulate the activity/expression of steroidogenic enzymes. These are expressed not only in the adrenal glands and gonads but also in many tissues that have the ability to convert circulating precursors into active hormones. In this way, EDCs may impact both on sexual differentiation and development and on hormone-dependent cancers. This review summarizes the evidence for EDCs as modulators of steroidogenic enzymes, identifies the structure/activity relationship in terms of inhibiting specific enzyme activity, questions whether experimental observations can equate with natural in vivo exposure or dietary intake of EDCs, and finally looks at the mechanisms through which these chemicals may disrupt normal steroidogenesis. In summarizing the evidence, the question of whether or not the dietary intake of these endocrine disrupters could pose a threat to human sexual development and health will be addressed.
Whitehead
Saffron A
SA
Department of Basic Medical Sciences, St George's University of London, Cranmer Terrace, London SW17 ORE, UK. saffron@sgul.ac.uk
Rice
Suman
S
D015067:17-Hydroxysteroid Dehydrogenases / Q000037:antagonists & inhibitors; D015096:3-Hydroxysteroid Dehydrogenases / Q000037:antagonists & inhibitors; D000818:Animals; D047072:Aromatase Inhibitors / Q000494:pharmacology; D003374:Coumarins / Q000494:pharmacology; D004032:Diet / Q000009:adverse effects; D052244:Endocrine Disruptors / Q000494:pharmacology*; D004781:Environmental Exposure / Q000009:adverse effects; D004968:Estrogens, Non-Steroidal / Q000494:pharmacology; D044950:Flavanones / Q000494:pharmacology; D047309:Flavones / Q000494:pharmacology; D012739:Gonadal Steroid Hormones / Q000096:biosynthesis*; D006801:Humans; D007529:Isoflavones / Q000494:pharmacology; D017705:Lignans / Q000494:pharmacology; D009183:Mycotoxins / Q000494:pharmacology; D010575:Pesticides / Q000494:pharmacology; D048789:Phytoestrogens / Q000494:pharmacology; D010968:Plasticizers / Q000494:pharmacology; D013329:Structure-Activity Relationship; D013429:Sulfatases / Q000037:antagonists & inhibitors; D015238:Sulfotransferases / Q000037:antagonists & inhibitors; D013501:Surface-Active Agents / Q000494:pharmacology
D047072:Aromatase Inhibitors; D003374:Coumarins; D052244:Endocrine Disruptors; D004968:Estrogens, Non-Steroidal; D044950:Flavanones; D047309:Flavones; D012739:Gonadal Steroid Hormones; D007529:Isoflavones; D017705:Lignans; D009183:Mycotoxins; D010575:Pesticides; D048789:Phytoestrogens; D010968:Plasticizers; D013501:Surface-Active Agents; D015067:17-Hydroxysteroid Dehydrogenases; D015096:3-Hydroxysteroid Dehydrogenases; C044256:3 (or 17)-beta-hydroxysteroid dehydrogenase; D015238:Sulfotransferases; D013429:Sulfatases