Regulation of δ‐Aminolevulinic Acid Synthetase by Drugs and Steroids <i>in vivo</i> and in Isolated Perfused Rat Liver

Abstract

δ‐Aminolevulinic‐acid‐synthetase induction by drugs depends upon the nutritional state of the animal. In allylisopropylacetamide‐treated animals the enzyme induction is reduced in fed compared with starved rats whereas after phenobarbital treatment an induction of the enzyme seen in starved animals is not observed in fed rats. δ‐Aminolevulinic‐acid‐synthetase induction is studied in relation to the synthesis of cytochrome P450. In the isolated rat liver perfused with either rat blood or washed bovine erythrocytes and Eagle minimal essential medium, δ‐aminolevulinic acid synthetase decreases sharply. This decrease can be prevented by the continuous addition of dexamethasone (9α‐fluoro‐16α‐methyl‐pregna‐1,4‐diene‐11β,17α,21‐triol‐3,20‐dione) or hydrocortisone (pregn‐4‐ene‐11β,17α,21‐triol‐3,20‐dione) but not by testosterone (androst‐4‐ene‐17β‐ol‐3‐one) or etiocholanolone (5β‐androstan‐3α‐ol‐17‐one). δ‐Aminolevulinic acid synthetase cannot be significantly induced by allylisopropyl‐acetamide unless corticoids are added to the perfusion medium. The results indicate that the synthesis of heme and, consequently, hemoproteins is controlled by corticoids or their metabolites in adult rat liver.