Heavy Metals Acting as Endocrine Disrupters

Endocrine disrupters are defined as chemical substances with either agonist or antagonist endocrine effects in human and animals. These effects may be achieved by interferences with the biosynthesis or activity of several endogenous hormones. Recently, it was demonstrated that heavy metals such as cadmium (Cd), arsen (As), mercury (Hg), nickel (Ni), lead (Pb) and zinc (Zn) may exhibit endocrine-disrupting activity in animal experiments. Emerging evidence of the intimate mechanisms of action of these heavy metals is accumulating. It was revealed, for example, that the Zn atom from the Zn fingers of the estrogen receptor can be replaced by several heavy metal molecules such as copper, cobalt, Ni and Cd. By replacing the Zn atom with Ni or copper, binding of the estrogen receptor to the DNA hormone responsive elements in the cell nucleus is prevented.

Insight:

For soft electrophiles such as mercury, the mechanism appears to primarily involve its highly specific irreversible inhibition of selenium dependent enzymes. Brain and endocrine tissues are very dependent on the uninterrupted availability of selenium for de novo synthesis of selenocysteine, the catalytic component at the active site of these enzymes. They have a multitude of functions including preventing and reversing oxidative damage, regulating thyroid hormone and calcium status, and various cell signalling pathways. The significance of selenium physiology in these tissues is not widely known, primarily because it is so well protected by homeostatic regulation that these tissues are invulnerable to almost all environmental insults. Currently, we know of only one exception. Mercury is uniquely able to prevent maternal selenium from being redistributed through the maternal/placental/fetal tissue pools. Meanwhile, since it readily transits both the placental and blood brain barriers, its ability to enter the fetal brain and irreversibly inhibit selenoenzyme activities and permanently sequester brain Se in the insoluble HgSe form is unmatched by other soft electrophiles. However, some of the other electrophiles may be just as capable as mercury at penetrating endocrine tissues and impairing selenoenzyme activities that are otherwise invulnerable to environmental insults. Selenium physiologists will soon be using soft electrophiles as a complementary way of evaluating the activities of various selenoenzymes in tissues since this approach is more readily titrated than doing genetic knockouts and can be applied in cases where genetic knockouts are lethal.

For more information, visit http://tinyurl.com/p8336ys