ToxSci Advance Access published online on September 15, 2008
Toxicological Sciences, doi:10.1093/toxsci/kfn191
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Molecular imaging, an innovative methodology for whole body profiling of endocrine disrupter action
,
* Laboratory of Biotechnology, Civic Hospital of Brescia, 25123 Brescia, Italy
Centre of Excellence on Neurodegenerative Diseases, University of Milan, 20133 Milan, Italy
To whom correspondence should be addressed. Corresponding author: Adriana Maggi, Department of Pharmacological Sciences, Via Balzaretti 9, 20133 Milan - Italy, e-mail: adriana.maggi{at}unimi.it, phone: +39 02 50318375, fax: +39 02 50318284
Received July 7, 2008; revision received September 4, 2008; accepted September 4, 2008
 |
Abstract |
|---|
Endocrine disrupters (EDs) are environment and food contaminants known to alter metabolic functions of mammals by interfering with specific endocrine pathways. Many EDs act on steroid hormone target cells by interacting with intracellular receptors (IRs) like estrogen receptors, androgen receptors, and thyroid hormone receptors; other receptors may be engaged. IRs are ligand-operated transcription factors acting in concert with general or cell-specific co-regulators. The newly acquired awareness on the panoply of IR functions has increased the concern on potential, unsought, harmful effects of EDs on human health and has questioned the capability of currently available methodologies to identify and study EDs in the environment and in the food chain. Indeed, current in vivo and in vitro methodologies restrict the analysis to very specific organs or cell systems, with obvious limitations in predicting the systemic metabolic consequences of ED exposure. The emphasis recently laid by Regulatory Authorities, including ECVAM, on the generation of in vitro model systems for toxicological analyses discouraged the development of models suitable to envision the whole spectrum of ED body actions required when studying compounds acting through IRs. Molecular imaging now provides the opportunity to quantify ED effects in living organisms enabling, for the first time, to acquire a full comprehension of the systemic effects of acute and prolonged exposure to EDs, solving the issue of the potential harm due to repeated low-dose exposure. The systems here reviewed are of unquestionable toxicological relevance and need to be taken into consideration to improve the methodology currently available and in use.
Key Words: reporter animals; optical imaging; endocrine disrupters; dietary estrogens; estrogen receptors; animal testing.