Steroid specificity of the glucocorticoid inhibition of amino acid transport in rat hepatoma cells.
Dexamethasone, a synthetic glucocorticoid, inhibits the initial rate of transport of the nonmetabolizable amino acid, alpha-aminoisobutyric acid, in rat hepatoma tissue culture (HTC) cells. To determine whether this inhibition is mediated by the same proximal steps as is the steroidal induction of tyrosine aminotransferase, we have examined the hormonal specificity of these two responses for various steroids previously characterized with respect to transaminase induction as agonists, partial agonists, antagonists, or inactive steroids. We conclude that the steroidal inhibition of amino acid transport, at steroid concentrations of 10(-5) M or less is mediated by the same glucocorticoid receptor mechanisms as the induction of tyrosine aminotransferase. First, the concentrations at which the full agonists, dexamethasone and cortisol, produce their half-maximal effects on phenomena are the same. Second, tetrahydrocortisol, which does not interact with the glucocorticoid receptor, neither inhibits transport nor induces transaminase. Third, the competitive interactions between partial agonists or antagonists and the full agonist dexamethasone with respect to both transport inhibition and enzyme induction are virtually identical. At concentrations greater than 10(-5)M, however, both partial agonist and antagonist steroids are capable of fully inhibiting amino acid transport. The effects of these steroids on transport, like those of dexamethasone, are reversible and are blocked by cycloheximide and actinomycin D. Furthermore, these steroids, like dexamethasone, slow the rate of efflux of alpha-aminoisobutyric acid from preloaded cells. Thus, the effects of high concentrations of partial agonist and antagonist steroids on amino acid transport do not appear to reflect a generalized toxic effect on membrane function.
D000621:Aminoisobutyric Acids / Q000378:metabolism*; D000818:Animals; D001692:Biological Transport / Q000187:drug effects; D002460:Cell Line; D003513:Cycloheximide / Q000494:pharmacology; D003609:Dactinomycin / Q000494:pharmacology; D003907:Dexamethasone / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004790:Enzyme Induction; D006908:Hydroxyprogesterones / Q000494:pharmacology; D007700:Kinetics; D008114:Liver Neoplasms, Experimental / Q000378:metabolism*; D011374:Progesterone / Q000494:pharmacology; D051381:Rats; D014444:Tyrosine Transaminase / Q000096:biosynthesis
D000621:Aminoisobutyric Acids; D006908:Hydroxyprogesterones; D003609:Dactinomycin; D011374:Progesterone; D003907:Dexamethasone; D003513:Cycloheximide; D014444:Tyrosine Transaminase