Enhancement of RNA Synthesis in Avian Liver Cell Cultures by a 5β-Steroid Metabolite During Induction of δ-Aminolevulinate Synthase

Abstract

The porphyrin-heme pathway is controlled in the liver at the level of the mitochondrial enzyme δ-aminolevulinate synthase (EC 2.3.1.37), a protein inducible in cultured avian hepatocytes by a variety of chemicals including certain 5β-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 Mn²⁺-(NH₄)₂SO₄-stimulated DNA-dependent RNA polymerase (EC 2.7.7.6) activities by the 5β-steroid metabolite, 3α-hydroxy-5β-androstan-17-one (etiocholanolone), in cultured avian hepatocytes during induction of the enzyme. These changes were demonstrated in the G₁ 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 δ-aminolevulinate synthase by steroid metabolites requires new RNA synthesis, very probably messenger RNA, suggesting a 5β-steroid transcriptional control mechanism for induction of this protein.

• 3α-hydroxy-5β-androstan-17-one and 2-allyl-2-isopropylacetamide action
• porphyrin-heme pathway
• RNA polymerases
• regulation
• protein synthesis