ABSTRACT

Thyroid hormones (TG) are known as modulators of signal transduction. Phospholipase D (PLD) is one of the TG targets in stimulated cells. Cell response to the short-term TG action is significantly reduced at old age. Taking into account that diacylglycerols (DAG) accumulation induces cell resistance to some regulatory factors in the target cells the study was aimed at determining if DAG accumulation in hepatocytes impairs L-thyroxine (LT₄)-induced activation of PLD.The effect of modulation of the endogenous DAG content in isolated hepatocytes on the short-term action of LT4 was studied. The experiments were performed on labeled by [¹⁴C] palmitic acid and [¹⁴C] oleic acid hepatocytes from 3- and 24-month-old rats under modulation of the DAG content. To evaluate the short-term LT₄ action on cells, the PLD activation was examined after 2 and 5 minutes of LT4 exposure to cells. The accumulation of DAG in the liver cells of old rats and in hepatocytes of young rats after their pre-treating with palmitic acid as a precursor has been found. Reduction of the DAG content in old and young hepatocytes cultivated in the presence of palmitic acid by the activation of DAG kinase with α-tocopherol acetate or as a result of a long-term exposure to LT4 is accompanied by improved ability of cells to respond adequately to the short-term hormone action. These results indicate that DAG plays an important role in the disorders of LT4-induced activation of phospholipase D, and the interaction of long- and short-term pathways for regulation of lipid metabolism in the liver exists.