STUDIES ON MECHANISM OF ESTROGEN BIOSYNTHESIS .V. STEREOCHEMICAL COMPARISON OF AROMATIZATION IN PLACENTAL AND MICROBIOLOGICAL SYSTEMS

1. 1. To provide definitive evidence as to whether 19-hydroxyandrost-4-ene-3,17-dione (I) may aromatize by similar mechanisms in human placental and in microbiological systems, the stereochemistry of hydrogen removal at C-1 in the conversion of I to estrogen was investigated. 2. 2. Incubations of 19-hydroxy-[1-3H(83%-β)]androst-4-ene-3,17-dione with a placental microsomal preparation and a NADPH-generating system gave estrone in which 84% of the tritium was lost, showing that the 1β-hydrogen was eliminated. When the NADPH-generating system was replaced by an artificial electron acceptor active in converting 19-hydroxyandrostenedione to estrone in microorganisms, no conversion to estrone was noted. 3. 3. Incubations of the same steroid substrate with respiring cultures of Pseudomonas sp. (ATCC 13262) and Nocardia restrictus showed that 22 and 28% of the tritium, respectively, was lost in the transformation to estrone, thus implicating removal of the α-hydrogen in the transformation. A similar result for N. restrictus was obtained with a 6000 × g supernate preparation and the artificial electron acceptor, phenazine methosulfate. 4. 4. The results show that the transformation of I to estrone in the two types of systems occurs by different stereochemical mechanisms, and that probably different electronic factors are involved also. © 1968.