Studies on the Secretion and Interconversion of the Androgens. II. Methods for Estimation of Rates of Secretion and of Metabolism from Specific Activities of Urinary Metabolites1

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Abstract
The application of isotope dilution techniques for the estimation of the rates of secretion and of metabolism of the C19 steroids, testosterone (T), androstenedione ([DELTA]), dehydroisoandrosterone (D) and dehydroisoandrosterone sulfate (DS), is discussed. The techniques considered involve the injection of tracers and the measurement of the specific activities of urinary metabolites. The following subjects are discussed: I) calculation of the secretory rates of D and DS; n) calculation of the rates of peripheral interconversion of D and DS; III) information derived from the isotope ratios in urinary dehydroisoandrosterone glucuronoside and DS and from expressions of the type R/a[centerdot]t after injection of H3-DS and C14-D; IV) calculation of the secretory rate of T, a) after the administration of labeled T, [DELTA], D and DS, and b) after the administration of labeled T and [DELTA]; V) calculation of the rates of interconversion and of metabolism to T and A; VI) information derived from the isotope ratios in urinary testosterone glucuronoside and androsterone glucuronoside and from expressions of the type Ra[centerdot]t after injection of H3-T and C14 -[DELTA] VII) calculation of the rate of conversion of D to [DELTA]; VIII) calculation of the secretory rate of A; and IX) estimation of the secretory rates and rates of peripheral interconversion of T, [DELTA], D and DS in a single experiment. This discussion of each of these subjects includes a description of the corresponding experimental design, the derivation of the formulae by which rates are calculated from the specific activities of the urinary metabolites and an analysis of the assumptions about pathways and sites of metabolism which are necessary to validate the calculations.