The Flux of Intermediates and Products in Aromatization of C19 Steroids by Human Placental Microsomes.

The appearance of intermediates and products in the transformation of 4-androstene-3,17-dione and testosterone to estrone and 17β-estradiol by human placental microsomes was studied. The variables investigated were time, temperature and the concentrations of reduced pyridine nucleotides and of testosterone. The relative amounts of metabolites were markedly influenced by all of the factors studied except temperature, although the reaction velocity at 37 °C was about twice that at 27 °C. Oxidoreduction at C-17 in starting material, intermediates and products was examined using a mixture of [4-14C]testosterone and [7β,17α-²H2]testosterone as substrate. Oxidation and reduction at C-17 was most prominent at the beginning and the end of the reaction sequence. 17α-Hydroxy-5α-androst-1-en-3-one was found to be an inhibitor of the C19 17β-hydroxysteroid dehydrogenase activity of human placental microsomes. [ABSTRACT FROM AUTHOR]