Induction of delta-aminolevulinic acid synthetase in isolated rat liver cells by steroids.
The role of steroids in regulation of delta-aminolevulinic acid synthetase has been studied in isolated rat liver cell suspensions under conditions previously shown to support inducation of the enzyme by drugs. Addition of a variety of C-19 and C-21 steroids to cell suspensions resulted, after 4 to 6 hours of incubation, in 2- to 5-fold increase in the activity of delta-aminolevulinic acid synthetase as measured in liver cell homogenates. The increase was prevented by cycloheximide. The most active steroid inducers tested were pregnene or pregnane derivatives with keto or hydroxyl groups at C-3 and C-20; in particular a beta-hydroxyl group at C-20 enhanced activity. These C-21 steroids at optimal initial concentrations caused 3- to 5-fold induction over 4 hours. A number of C-19 androstene and androstane compounds caused 2- to 3-fold inducation over the same period. Hydrocortisone had no effect. For a variety of androstane and pregnane derivatives, inducation by 5alphaH steroids was as great as or greater than that by 5betaH compounds, in contrast to previous findings in chick embryo liver. Induction of delta-aminolevulinic acid synthetase by steroids in isolated liver cells was shown to be subject to feedback repression by hemin.
D000624:5-Aminolevulinate Synthetase / Q000096:biosynthesis*; D000731:Androstanes / Q000494:pharmacology; D000736:Androstenes / Q000494:pharmacology; D000818:Animals; D003513:Cycloheximide / Q000494:pharmacology; D004790:Enzyme Induction / Q000187:drug effects; D006427:Hemin / Q000494:pharmacology; D006728:Hormones / Q000494:pharmacology*; D066298:In Vitro Techniques; D007700:Kinetics; D008099:Liver / Q000187:drug effects / Q000201:enzymology*; D011278:Pregnanes / Q000494:pharmacology; D011283:Pregnenes / Q000494:pharmacology; D051381:Rats; D013256:Steroids / Q000494:pharmacology*; D013329:Structure-Activity Relationship; D013997:Time Factors
D000731:Androstanes; D000736:Androstenes; D006728:Hormones; D011278:Pregnanes; D011283:Pregnenes; D013256:Steroids; D006427:Hemin; D003513:Cycloheximide; D000624:5-Aminolevulinate Synthetase