Receptors mediating toxicity and their involvement in endocrine disruption.
Many toxic compounds exert their harmful effects by activating of certain receptors, which in turn leads to dysregulation of transcription. Some of these receptors are so called xenosensors. They are activated by external chemicals and evoke a cascade of events that lead to the elimination of the chemical from the system. Other receptors that are modulated by toxic substances are hormone receptors, particularly the ones of the nuclear receptor family. Some environmental chemicals resemble endogenous hormones and can falsely activate these receptors, leading to undesired activity in the cell. Furthermore, excessive activation of the xenosensors can lead to disturbances of the integrity of the system as well. In this chapter, the concepts of receptor-mediated toxicity and hormone disruption are introduced. We start by describing environmental chemicals that can bind to xenosensors and nuclear hormone receptors. We then describe the receptors most commonly targeted by environmental chemicals. Finally, the mechanisms by which receptor-mediated events can disrupt the system are depicted.
Rüegg
Joëlle
J
Department of Biosciences and Nutrition, Karolinska Institutet, Huddinge, Sweden. joelle.ruegg@ki.se
Penttinen-Damdimopoulou
Pauliina
P
Mäkelä
Sari
S
Pongratz
Ingemar
I
Gustafsson
Jan-Ake
JA
D000818:Animals; D052244:Endocrine Disruptors / Q000633:toxicity*; D004703:Endocrine System / Q000187:drug effects* / Q000378:metabolism / Q000502:physiology; D006801:Humans; D008954:Models, Biological; D018160:Receptors, Cytoplasmic and Nuclear / Q000378:metabolism* / Q000502:physiology; D015398:Signal Transduction / Q000187:drug effects; D015262:Xenobiotics / Q000633:toxicity
D052244:Endocrine Disruptors; D018160:Receptors, Cytoplasmic and Nuclear; D015262:Xenobiotics