Studies on the Secretion and Interconversion of the Androgens. III. Results Obtained After the Injection of Several Radioactive C19Steroids, Singly or as Mixtures1

Abstract

In an attempt to obtain information not otherwise available about the complex problem of androgen secretion in the human subject, various experiments involving the administration of isotopically labeled steroids have been carried out. The experiments consisted of injecting various steroids labeled with C14 or H3, singly or in combination, into various subjects and isolating appropriate metabolites from their urine. The C19 steroids used as tracers were dehydroisoandrosterone (D), dehydroisoandrosterone sulfate (DS), androstenedione ([DELTA]) and testosterone (T). After the administration of labeled D it was observed that the specific activities of the urinary glucuronoside of D (DG) were higher than the specific activities of urinary DS, androsterone (A) and etiocholanolone (E). The comparison of these specific activities indicated the existence of secreted precursors, other than D, for DS, A and E (DS itself for DS and T or A for A and E). When tracers of D and DS labeled with H3 and C14 were simultaneously administered, the H3/C14 ratios were different in DG and DS, whereas the ratios in DG and in the conjugates of A and E were practically equal. This indicates that DG, A and E have D as a common metabolic precursor. After in injection of a mixture of tracers of T and [DELTA] labeled with H3 and C14, the H3/C14 ratios in androsterone glucuronoside were different from the ratios in the glucuronoside of T. These observations gave information about the pathways of metabolism of the C19 steroids and suggested an experimental design which permits the evaluation of the rates of secretion and metabolism of T, [DELTA], D and DS after a single injection of a mixture of tracers of T, D and DS, labeled with H3 and C14. Rates of secretion and of peripheral metabolism of the C19 steroids were calculated from the data obtained in this study. The formulae used have been presented in an accompanying paper in which the assumptions necessary to validate the calculations were analyzed.