Metabolic Precursors of Urinary Dehydroisoandrosterone

Abstract

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

Chemical Structure of Steroids in Relation to Promotion of Growth of the Vagina and Uterus of the Hypophysectomized Rat

“…In the absence of further knowledge, however, it is reasonable to assume that the most active compounds in a closely related series possess groups in a state which actually functions biologically, whereas the less active compounds may first be transformed to the active structures. Lieberman and Teich (22) have made the generalization that, when changes occur during metabolism, steroids are usually transformed chemically to a more highly reduced state.…”

Studies in Cushing's Syndrome. Iii. Urinary 17-Ketosteroids in Patients With Bilateral Adrenal Cortical Hyperplasia*

“…Recent studies suggest that abnormally large quantities of dehydroisoandrosterone are by no means invariably found in adrenal cortical carcinoma (32). Be-cause the precursor (or precursors) of dehydroisoandrosterone is unknown at this time, the true significance of this steroid as a urinary excretory product is difficult to assess (33,34).…”

Changes in the Excretion Pattern of Neutral 17-Ketosteroids During Oestrogen Administration to Male Subjects

“…One may, however, consider the possibility of a direct action on the adrenal cortex by the oestrogen, particularly as certain steroids have been shown to have a direct stimulatory influence on adrenocortical metabohsm [Brummel, Halkerston & Reiss, 1954]. Lieberman & Teich [1953] have suggested that DHA might arise from 5:3ß: 17-diol C21 metabolites derived from intermediates in the biogenesis of the corticosteroids by hydroxylation at C17 prior to conversion of the A5:3/? : 17-diol group to a A4:3-ketone.…”