Nuclear all-trans retinoic acid receptor status in rat liver: A comparisonof effects of three different stressors - Immobilization, laparotomy, and 2-deoxy-D-glucose

Retinoic acids and their cognate nuclear receptors exert a substantial regu latory role in cell growth and development as well as in the neuroendocrine system. These effects are primarily mediated by all-trans retinoic acid re ceptors (RARs), members of the steroid/thyroid hormone receptor superfamily of ligand inducible transcription factors. The present study was undertake n in order to compare the effects of immobilization stress (IMO), laparotom y, and 2-deoxy-D-glucose (2DG)-induced intracellular glucopenia on both nuc lear RAR affinity and concentration in the rat liver. IMO when compared to non-stressed group of rats, significantly reduced the RAR maximal binding c apacity (B-max) in liver, with the equilibrium association constant (K-a) r emaining unchanged. No significant changes of the RAR B-max and the K-a, we re observed in liver of rats that underwent laparotomy. In contrast, a sing le dose of 2DG (500 mg/kg) resulted in a significant increase of the RAR B- max, 10 h after 2DG application, with the K-a remaining unchanged. Shorter intervals, 1 or 5 h after 2DG application were ineffective on both the RAR B-max and K-a. In the 2DG-adapted rats (6 doses of 2 DG, 500 mg/kg; 1 dose/ day), decapitated 24 h after the last 2DG dose, the RAR B-max was found sig nificantly higher when compared to control group of animals. No further eff ect of the next dose of 2DG to repeatedly injected rats on the RAR B-max an d K-a was observed in animals killed 5 h after the seventh dose of 2DG. 2DG -induced intracellular glucopenia markedly up-regulates RARs in liver, but does not change the affinity of the receptor. Thus, the effect of 2DG on RA R concentration in liver specifically differs from that of IMO or laparotom y.