Potential Toxicity of Organotin Compounds via Nuclear Receptor Signaling in Mammals

摘要

Organotin compounds have been widely used as agricultural fungicides, rodent repellents, and molluscicides and in antif ouling paints for ships and fishing nets. These widespread uses have resulted in the release of increasing amounts of organotins into the environment. In aquatic invertebrates, particularly marine gastropods, organotin compounds, such as tributyltin (TBT) and triphenyltin (TPT), induce irreversible sexual abnormality in females which is termed "imposex" at very low concentrations. Although it has been theorized that these compounds act as potential competitive inhibitors of aromatase, which converts androgen to estrogen, and then increase levels of unconverted androgens in gastropods, their effective concentrations for aromatase inhibition are high. In addition to wildlife, organotins may have various undesirable effects on human health. In human ovarian granulosa cells, these compounds suppress aromatase activity at the nanomolar level. Contrary to this, in human choriocarcinoma cells, these compounds markedly enhance estrogen biosynthesis along with the increase of aromatase activity at the same low concentrations. Although there are many reports describing the potential toxicity of organotins, the critical target molecules for the toxicity of organotin compounds remain unclear. New data identify TBT and TPT as nanomolar agonist ligands for retinoid X receptor (RXR) and peroxisome proliferator-activated receptor (PPAR) gamma, which are members of the nuclear receptor superfamily. Here, we review the potential toxicity of organotin compounds via these nuclear receptors in mammals.