A structural view of nuclear hormone receptor: endocrine disruptor interactions

作者：le Maire Albane; Bourguet William^*; Balaguer Patrick

来源：Cellular and Molecular Life Sciences, 2010, 67(8): 1219-1237.

DOI：10.1007/s00018-009-0249-2

• Nuclear hormone receptors
• Endocrine-disrupting chemicals
• Environmental pollutants
• Crystal structures
• Hormone

Endocrine-disrupting chemicals (EDCs) represent a broad class of exogenous substances that cause adverse effects in the endocrine system by interfering with hormone biosynthesis, metabolism, or action. The molecular mechanisms of EDCs involve different pathways including interactions with nuclear hormone receptors (NHRs) which are primary targets of a large variety of environmental contaminants. Here, based on the crystal structures currently available in the Protein Data Bank, we review recent studies showing the many ways in which EDCs interact with NHRs and impact their signaling pathways. Like the estrogenic chemical diethylstilbestrol, some EDCs mimic the natural hormones through conserved protein-ligand contacts, while others, such as organotins, employ radically different binding mechanisms. Such structure-based knowledge, in addition to providing a better understanding of EDC activities, can be used to predict the endocrine-disrupting potential of environmental pollutants and may have applications in drug discovery.

• 出版日期2010-4