Relation of steroid structure to enzyme induction in hepatoma tissue culture cells

Differences in steroid behaviour do not appear to result from differences in steroid uptake or metabolism, or from an effect on general cell protein synthesis or degradation of enzyme, as well as the interaction of these steroids with an allosteric receptor system concerned with the regulation of synthesis of enzyme.

Abstract

Glucocorticoid hormones induce an increase in the rate of synthesis of the enzyme tyrosine aminotransferase in hepatoma tissue culture cells. On the basis of an examination of steroid concentration and structure with regard to induction of enzyme, we have classified a wide variety of steroids into four groups: (1) optimal inducers (e.g. cortisol, dexamethasone and corticosterone) which induce the enzyme to a maximal level; (2) sub-optimal inducers (e.g. 11β-OH progesterone, 11-deoxycortisol, and deoxycorticosterone) which induce the enzyme to a sub-maximal but characteristic level and competitively inhibit induction by optimal inducers; (3) anti-inducers (e.g. testosterone, 17α-methyltestosterone) which cannot induce the enzyme, but can competitively inhibit induction by optimal- and sub-optimal inducers; and (4) inactive steroids which neither induce nor inhibit enzyme induction. These differences in steroid behaviour do not appear to result from differences in steroid uptake or metabolism, or from an effect on general cell protein synthesis or degradation of enzyme. We interpret our findings in terms of the interaction of these steroids with an allosteric receptor system concerned with the regulation of synthesis of enzyme.