Enhancement of RNA synthesis in avian liver cell cultures by a 5beta-steroid metabolite during induction of delta-aminolevulinate synthase.

The porphyrin-heme pathway is controlled in the liver at the level of the mitochondrial enzyme delta-aminolevulinate synthase (EC 2.3.1.37), a protein inducible in cultured avian hepatocytes by a variety of chemicals including certain 5beta-metabolites of steroid hormones. The great sensitivity of the induction process to inhibition by agents known to block transcriptional activity of genetic material suggests that some control mechanism may be operating at this level to regulate the formation of the enzyme. We report here enhancement of nuclear RNA synthesis and of Mn(2+)-(NH(4))(2)SO(4)-stimulated DNA-dependent RNA polymerase (EC 2.7.7.6) activities by the 5beta-steroid metabolite, 3alpha-hydroxy-5beta-androstan-17-one (etiocholanolone), in cultured avian hepatocytes during induction of the enzyme. These changes were demonstrated in the G(1) phase of the hepatocyte cell cycle at a time when DNA synthesis is constant. Our findings support the view that one of the early steps in the process of induction of delta-aminolevulinate synthase by steroid metabolites requires new RNA synthesis, very probably messenger RNA, suggesting a 5beta-steroid transcriptional control mechanism for induction of this protein.