DEPLETION OF ARYLHYDROCARBON RECEPTOR DURING ADIPOSE DIFFERENTIATION IN 3T3-L1 CELLS

Arylhydrocarbon receptor (AhR) is the receptor for 2,3,7,8-tetrachloro dibenzo-p-dioxin (TCDD) and related compounds. Although a physiologica l ligand for AhR has yet to be identified, several lines of evidence s uggest that AhR may play an important role not only in the regulation of xenobiotic metabolism but also in the maintenance of homeostatic fu nctions. When TCDD is administrated in vivo, this compound is primaril y deposited in adipose tissue. Therefore, it is critical to know the s tates of AhR in adipose cells for assessing the expression of toxiciti es of TCDD and related compounds in vivo. In this report, we examined the levels of AhR protein and its associated protein (Arnt) during the adipose differentiation in 3T3-L1 cells. The level of AhR protein was found to decrease with ongoing adipose differentiation in 3T3-L1 cell s. The binding activity to the xenobiotic response element and the cel lular response to TCDD were also lowered as a result of adipose differ entiation. These results indicate that the depletion of AhR is a novel event associated with adipose differentiation in 3T3-L1 cells and tha t the magnitude of the depletion of AhR is sufficient for 3T3-L1 cells to lose the functional response to xenobiotics. We also found a popul ation of 3T3-L1 cells which have an adipose differentiation capability in the presence of high doses of TCDD. These cells lack nuclear AhR b ut not cytoplasmic AhR, suggesting a possible negative role of ligande d nuclear AhR in adipose differentiation. The level of the Amt protein also decreased as a result of the differentiation. However, the patte rn of the depletion of the Arnt protein was distinct from that of the AhR protein. The data presented in this study will provide opportuniti es to carry out studies to better understand the roles of AhR in adipo se cells which are the primary targets of TCDD. (C) 1998 Academic Pres s.