E VER since dehydroisoandrosterone was first isolated from human urine in 1934 (1) the riddle of its precursor has plagued the biochemist and the clinician. Since it has recently been shown that dehydroisoandrosterone is excreted in normal urine in much larger amounts than hitherto recognized, and therefore that this substance is an important index of normal as well as abnormal adrenal cortical activity, the question of its precursor has assumed added importance. Especially is this true since the estimation of urinary dehydroisoandrosterone is probably as significant for evaluating adrenal cortical function as the determination of urinary corticoids.It is unnecessary to dwell upon the reasons why earlier workers reported low excretion values (of the order of 0.2 mg. /day) (2) in the urine of normal men and women. It is well recognized now that vigorous acid hydrolysis alters a sensible fraction of the dehydroisoandrosterone sulfate present in any urine, resulting in an underestimation of the actual concentrations. Nevertheless a recent paper by Landau et al. (3) reported that normal men and women excreted 1.0-12.4 mg./twenty-four hours, or 10-60 per cent of the total ketosteroids, even when using a l^drolytic procedure consisting of boiling with acid for fifteen minutes. Dingemanse et al. (4) estimated from a chromatographic analysis of the urinary 17-ketosteroids that normal women excreted on the average 1.4 mg. of dehydroisoandrosterone daily (about 30 per cent of the total ketosteroids) and normal men, 2.6 mg. of the steroid daily (about 50 per cent of the total). Using a mild method of acid hydrolysis, Ronzoni (5) isolated the ketonic, digitoninprecipitable fraction and measured its deh}^droisoandrosterone content by the Allen test (6). By this procedure she estimated the normal excretion of this adrenal metabolite to be 2.2-5.0 mg./twenty-four hours or 15-26 per cent of the total 17-ketosteroids.Although attempts have been made to examine certain steroids as possible precursors of urinary dehydroisoandrosterone, the nature of these precursors remains obscure. In spite of the superficial similarity in chemical structure between the hormone, testosterone, and the metabolite, dehydroisoandrosterone, it was recognized early that the hormone was not the 1140
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