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

Retinoic acids and their cognate nuclear receptors exert a substantial regulatory role in cell growth and development as well as in the neuroendocrine system. These effects are primarily mediated by all-trans retinoic acid receptors (RARs), members of the steroid/thyroid hormone receptor superfamily of ligand inducible transcription factors. The present study was undertaken in order to compare the effects of immobilization stress (IMO), laparotomy, and 2-deoxy-D-glucose (2DG)-induced intracellular glucopenia on both nuclear RAR affinity and concentration in the rat liver. IMO when compared to non-stressed group of rats, significantly reduced the RAR maximal binding capacity (B-max) in liver, with the equilibrium association constant (K-a) remaining unchanged. No significant changes of the RAR B-max and the K-a, were observed in liver of rats that underwent laparotomy. In contrast, a single 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 significantly higher when compared to control group of animals. No further effect of the next dose of 2DG to repeatedly injected rats on the RAR B-max and 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 RAR concentration in liver specifically differs from that of IMO or laparotomy.