MOLECULAR CHARACTERIZATION OF MOUSE 17-BETA-HYDROXYSTEROID DEHYDROGENASE-IV

17 beta-hydroxysteroid dehydrogenases (17 beta-HSD) catalyze the conve rsion of estrogens and androgens at the C17 position. The 17 beta-HSD type I, II, III and IV share less than 25% amino acid similarity. The human and porcine 17 beta-HSD N reveal a three-domain structure unknow n among other dehydrogenases. The N-terminal domains resemble the shor t chain alcohol dehydrogenase family while the central parts are relat ed to the C-terminal parts of enzymes involved in peroxisomal beta-oxi dation of fatty acids and the C-terminal domains are similar to sterol carrier protein 2. We describe the cloning of the mouse 17 beta-HSD I V cDNA and the expression of its mRNA. A probe derived from the human 17 beta-HSD IV was used to isolate a 2.5 kb mouse cDNA encoding for a protein of 735 amino acids showing 85 and 81% similarity with human an d porcine 17 beta-HSD IV, respectively. The calculated molecular mass of the mouse enzyme amounts to 79,524 Da. The mRNA for 17 beta-HSD IV is a single species of about 3 kb, present in a multitude of tissues a nd expressed at high levels in liver and kidney, and at low levels in brain and spleen. The cloning and molecular characterization of murine , human and porcine 17 beta-HSD IV adds to the complexity of steroid s ynthesis and metabolism. The multitude of enzymes acting at C17 might be necessary for a precise control of hormone levels.