[Autogenic regulation of the sensitivity of liver cells to glucocorticoids during prolonged hormonal stimulation].
The mechanisms of reversible decrease of hormone-dependent induction of tyrosine aminotransferase (TAT) by rat liver cells after prolonged administration of the glucocorticoid was studied. It was shown that the main links of the glucocorticoid action mechanism (i.e., the formation of a cytoplasmic hormone-receptor complex and the hormone accumulation in the nuclei) do not change under these conditions. It was found also that one of the necessary prerequisites for the decrease of the hormone-dependent induction of TAT is the constant production by liver cells of large amounts of TAT irrespective of whether this process is induced by the glucocorticoid or by a non-hormonal inducer, e.g., tryptophan. Using the dot-hybridization technique, it was demonstrated that the inhibition of hormone-dependent induction of TAT is correlated with the reduction of mRNA TAT. It was supposed that the main links in the mechanism of inhibition of the hormone-dependent induction are the formation of a large excess of the inducible protein--TAT--in the cells as well as the accumulation of end products of the TAT-catalyzed transamination reaction which cause a feed-back repression of the de novo synthesis of TAT. Studies with cell cultures of Morris hepatoma which is known to be sensitive to glucocorticoids revealed the ability of glucose, the end product of gluconeogenesis reactions, to provide for selective inhibition of the hormone-induced accumulation of mRNA TAT in hepatoma cells.
D000315:Adrenalectomy; D000818:Animals; D004790:Enzyme Induction; D006854:Hydrocortisone / Q000378:metabolism / Q000494:pharmacology*; D008099:Liver / Q000187:drug effects* / Q000201:enzymology; D008114:Liver Neoplasms, Experimental / Q000201:enzymology; D008297:Male; D051381:Rats; D011919:Rats, Inbred Strains; D011965:Receptors, Glucocorticoid / Q000187:drug effects / Q000378:metabolism; D013997:Time Factors; D014364:Tryptophan / Q000494:pharmacology; D014444:Tyrosine Transaminase / Q000096:biosynthesis*
D011965:Receptors, Glucocorticoid; D014364:Tryptophan; D014444:Tyrosine Transaminase; D006854:Hydrocortisone
Autogennaia reguliatsiia chuvstvitel'nosti kletok pecheni k gliukokortikoidam v usloviiakh dlitel'noĭ gormonal'noĭ stimuliatsii.