METABOLISM OF 11β-HYDROXY-Δ4-ANDROSTENE-3, 17-DIONE IN MAN

This study describes the metabolism and fate of an intravenous tracer dose of 1 I/?-hydroxy-A"-androstene-3, 17-dione-4-Cl4 (I).The compound studied is a primary adrenal secretory product (l-3) chemically related to hydrocortisone but different from that adrenal hormone in that the ketol side chain has been replaced by a simple ketone.Knowledge of the metabolism of this substance and the dynamics of its transport is of value for a number of reasons: (1) The compound is almost certainly a precursor of certain 11-oxygenated Cl9 steroids found in urine.Therefore the end products and especially their quantitative relationship should provide an opportunity to evaluate the extent to which glandular production of this hormone contributes to the urinary steroid pattern.(2) The compound might be a precursor of Cl9 11-deoxy urinary steroids.If this were the fact, the most reasonable end products would be 3a-hydroxyandrostane-17-one and 3a-hydroxyetiocholane-17-one and, therefore, the extent to which these were formed should be a measure of the biochemical removal of the oxygen at C-11.The inability of the body to form these metabolites, on the other hand, should provide presumptive evidence that an oxygen atom at C-11 remains attached to the steroid nucleus throughout the biochemical transformation of steroid hormones.(3) A comparison of this compound with hydrocortisone was of interest in order to explore the possibility that structurally similar hormones undergo a similar distribution and metabolic fate.(4) K nowledge of the absolute and relative amounts of 5/3 and 5cu metabolites derived from this compound would provide a test of Dorfman's hypothesis that the chemical nature and quantity of hormone produced by a gland can be inferred from calculations based on the amount and stereoisomeric ratio of metabolites in the urine.It has been found that approximately 80 per cent of the total urinary metabolites of (I) can be accounted for as four 11-oxygenated 17-ketosteroids of the androstane and etiocholane series (Fig. 1).So significant amount of 11-deoxy compounds was found among the metabolites of this hormone.Compound I was transported, metabolized, and excreted in a