The hepatic glucocorticoid domain: evidence for early and late hormone-mediated changes in the synthesis of individual protein gene products.
Studies were conducted to determine the extent of rapidly evolving effects of glucocorticoids on the transcriptional activity of individual hepatocyte genes through comparisons of the relative rates of synthesis of the more than 3000 protein gene products that are resolved in giant two-dimensional separatory gels. During the first 20 h in primary culture normal hepatocytes displayed substantial spontaneous changes in over 80 proteins. One effect of an added glucocorticoid, dexamethasone, was to retard or reverse the progression of roughly half of these. However, such long-term hormone treatment also caused 27 inductions and 26 repressions, many of which occurred in proteins that do not change spontaneously. Some of these coincide with the previously reported glucocorticoid domain of hepatoma cells. In contrast to such long-term changes, short-term (4 h) incubation with dexamethasone induced 10 proteins and repressed 6 others. Five of these early hormone inductions and all of the early repressions were maintained or enhanced by 20 h. However, the remaining five early glucocorticoid inductions appeared to be transient, since by 16-20 h the effects were either markedly reduced or absent. These results show the existence of an early glucocorticoid domain, qualitatively different from that seen at later times, which may be more representative of the primary steroid hormone responses.
D000818:Animals; D003907:Dexamethasone / Q000494:pharmacology*; D004591:Electrophoresis, Polyacrylamide Gel; D005796:Genes / Q000187:drug effects*; D007700:Kinetics; D008099:Liver / Q000187:drug effects / Q000378:metabolism*; D008297:Male; D008970:Molecular Weight; D011506:Proteins / Q000235:genetics / Q000302:isolation & purification; D051381:Rats; D011919:Rats, Inbred Strains; D014158:Transcription, Genetic / Q000187:drug effects*
D011506:Proteins; D003907:Dexamethasone