METABOLISM OF Δ4-ANDROSTENE-3β, 17β-DIOL AND Δ4-ANDROSTENE-3α, 17β-DIOL IN VITRO

Several schemes proposed for the catabolism of testosterone in vivo involve variations in the sequence of reduction of the Cd-5 double bond and the carbonyl at CO, and oxidation at CU.The sequence involving the initial oxidation of the 17b-hydroxy group, followed by the reduction of the double bond and the 3-ketone to give androsterone and etiocholanolone, has received some verification and has been adequately reviewed (1, 2).However, little evidence of a direct nature has been presented to include or exclude other possible metabolic pathways.For example, a second scheme would involve the primary reduction of the 3-carbonyl group of testosterone to give A4-androstene-3a, 17@-diol and A4-androstene-3/3, 17j3diol with subsequent reduction of the double bond and oxidation at Cl,.The relative importance of this pathway could be assessed by investigating the formation of the products of these steroids obtained by in vitro and in viva techniques.A4-Androstene-3P, 17j3-dioll and A4-androstene-3a, 17b-dial, and the t,wo corresponding 4-C14-labeled compounds, were synthesized and incubated with liver tissue.The major products of the incubat,ion were quantitatively estimated following paper chromatography by calorimetric and spectrophotometric assay and by the determination of the radioactive content in the constituents.The results indicate that the two dials are not in the direct pathway of testosterone catabolism. MethodsSynthesis of A4-Androstene-@ , 1 Y/3-diol and A4-Androstene-& , i7&diol--Testosterone and testosterone+Cl4 (30 PC. per mmole), prepared according t,o the method of Fujimoto (3), were reduced with sodium boron hydride