Abstract
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.
Highlights
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 &fold increase in the activity of &aminolevulinic acid synthetase as measured in liver cell homogenates
Under similar conditions it was shown that the drug allylisopropylacetamide caused induction of ALA synthetase quantitatively comparable to that obtained with the drug in uiuo in starved rats; such induction could be reproducibly observed only in cell suspensions supplemented with dibutyryl cyclic AMP [15]
We have shown that a variety of naturally occurring steroids are capable of inducing ALA synthetase by direct action on mammalian liver cells
Summary
Choice of Experimental Conditions-In previous papers we described conditions for cell isolation and incubation appropriate for studies of enzyme induction in suspensions of isolated rat liver cells. Under similar conditions it was shown that the drug allylisopropylacetamide caused induction of ALA synthetase quantitatively comparable to that obtained with the drug in uiuo in starved rats; such induction could be reproducibly observed only in cell suspensions supplemented with dibutyryl cyclic AMP [15]. I compares the effects of a range of steroids in the presence of dibutyryl cyclic AMP on the level of ALA synthetase in isolated liver cells in a I-hour incubation period. 1 shows the relationship between initial steroid concentration and induction of ALA synthetase in liver cell suspensions over a 4-hour incubation period.Curves for four typical steroid inducers are shown. Preliminary experiments have suggested that the same is true for induction by steroids, but this point remains to be clarified
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