Endocrine Abstracts

The parallel increase in the amount of environmental contaminants and in the prevalence of some human diseases has led to a growing interest in understanding how these compounds, so-called endocrine disruptors, may affect human health. In this scenario, the concept that obesity is the result of the interplay of genetic and lifestyle factors has been changing due to the growing evidence that environmental contaminants might alter endocrine function.

Organostannics are a distinct class of organic pollutants related to paints used in overseas transports and agrotoxics, and have emerged as potential metabolic disruptors due to their effects on nuclear receptors. Tributyltin (TBT) was the organostannic compound studied and has been shown to be a strong agonist for peroxisome proliferator-activated receptor-γ (PPARγ) and stimulate adipogenesis, with the potential to induce weight gain and other unfavorable effects of strong PPARγ activation. However, little is known about the effect of other organostannic compounds on this receptor.

In this study, we describe the agonist effects of the organostannic pollutants dibutyltin dilaurate (DBT) and benzoate TBT on PPARγ in HeLA and human mesangial cells cotransfected with PPARγ-GAL4 and the UAS-tk-luc reporter. This effect appeared to be specific for PPARγ, since DBT, benzoate TBT and also TBT had no activity on glucocorticoid, estrogen and thyroid hormone receptors when assessed by reporter gene assays using the respective expression vectors and responsive element-driven luciferase reporter.

Further studies are being carried out to investigate the effect of these compounds on cell-based adipogenesis, PPARγ-responsive genes and also in vivo. Additionally, we seek to investigate their mode of binding to the binding pocket of PPARγ. These results may provide a better understanding of how these pollutants affect in human health and possibly the increasing rates of obesity and its associated diseases worldwide.