Hildegard Wilson

Use of periodate oxidation in the clinical analysis of urine corticoids

Abstract A method for the routine clinical determination of urinary 17-hydroxy-corticoids is described and its reliability analyzed. The method consists of reduction with potassium borohydride followed by oxidation with sodium metaperiodate as described by Few, extraction with ether, and performance of the Zimmermann reaction. The advantages of this method are greater specificity of the oxidant, the avoidance of hot acid hydrolysis, the technical simplicity, and the removal of interfering chromogens from the final Zimmermann color.

THE METABOLISM OF DESMOSTEROL IN HUMAN SUBJECTS DURING TRIPARANOL ADMINISTRATION

Recent studies with triparanol (1-[p-,3-diethylaminoethoxyphenyl ]-1(p-tolyl) -2(p-chlorophenyl)ethanol) have demonstrated that this compound inhibits cholesterol biosynthesis by blocking the reduction of 24-dehydrocholesterol (desmosterol) to cholesterol (2-4). Administration of triparanol to laboratory animals and to man results in the accumulation of desmosterol in the plasma and tissues, usually with some concomitant lowering of the plasma total sterol concentration (2, 5). In studies with human subjects it was observed that after about 2 weeks the desmosterol concentration tended to plateau at an average level of 27 per cent of the total circulating sterols (5). The ratios of desmosterol to cholesterol in animal tissues (2) differed somewhat from the ratios in plasma. In addition, injection of the cholesterol precursor 2-C14-mevalonic acid during triparanol administration resulted in the rapid appearance of labeled desmosterol in blood, while no significant radioactivity appeared in cholesterol in the first few days (5). The object of the present experiments was to study the metabolism of desmosterol in patients receiving triparanol. Since cholesterol serves as the biosynthetic precursor for several physiologically important compounds, including bile acids and steroid hormones, the question arose whether desmosterol could also function as a precursor for these compounds without first being transformed into cholesterol. The studies reported herein demonstrate the direct conversion of desmosterol to both bile acids and to steroid hormones, and also provide information about the over-all metabolism of this sterol in the triparanol-treated man.

A simplified procedure for the estimation of testosterone production rates

Abstract A relatively simple method for the isolation of testosterone from urine, which results in a fraction pure enough for either fluorometric assay or gas-liquid chromatography is described.

Absorption spectra of Δ5-3β -hydroxy steroids in several sulfuric acid reagents

Abstract Absorption spectra between 200 and 700 mμ of eleven Δ5-3β-OH steroids have been determined at room temperature in the Allen and Oertel ethanolic sulfuric acid reagents, and in concentrated sulfuric acid. All but three of these steroids gave typical high peaks near 408 mμ with either ethanolic reagent. Those three had other characteristic peaks. Δ5-Pregnere-3β,17α,20α-triol showed an unusual play of colors with the Allen reagent, turning deep violet-blue in 30–40 min. The ethanolic reagents, particularly that of Allen, provide means for the simultaneous identification and determination of these Δ5-3β-OH steroids. Distinctive curves were given by a number of other steroids as well. The reagents are useful for locating reactive compounds on paper chromatograms and in column eluates.

On the role of androstenedione and testosterone as precursors of urinary androsterone and 5β-androsterone

Abstract The 3 H/ 14 C ratios in urinary androsterone and 5β-androsterone have been determined after i.v. administration of testosterone- 14 C and 4-androstene-3, 17-dione- 3 H. Eight of 19 subjects showed significant differences in ratios in these two metabolites. Enrichment with 14 C counts from testosterone occurred in either isomer. These data indicate that urinary androsterone and 5β-androsterone are not uniquely derived from a single plasma androstenedione pool to which both testosterone and dehydroepiandrosterone contribute.

REVERSIBLE ADRENAL UNRESPONSIVENESS IN A PATIENT WITH CONGENITAL ADRENAL HYPERPLASIA

A 7 1/2‐year‐old boy in whom the diagnosis of congenital adrenal hyperplasia was made at age 5 weeks is presented. Treatment with exogenous corticoids was started immediately, but between ages 1 to 4 an Addisonian state intervened. Classical congenital adrenal hyperplasia then reappeared after age 6, following a reduction in corticoid replacement. Suppression of ACTH by exogenous glucucorticoid is suggested as a possible cause of this reversible adrenal failure.