The Fate of Hydrocortisone-4-C14 in Man 1

Abstract

This study deals with the dynamic behavior of hydrocortisone in man and the relationship of the metabolic fate of this principal adrenal hormone to the physiologic or pathologic state of the experimental subject. The period during which the hormone persists in the tissues, the rate of its excretion, and the relationship between the two have been measured by precise and discriminating methods. Furthermore, the details of the metabolic transformations and the rate at which these occur have been discussed and correlated with some known biologic effects of the hormone. These studies have been possible as a result of the availability of ring A labeled hydrocortisone through a cooperative effort sponsored by the Endocrinology Study Section of the U. S. Public Health Service (1).Previous work in our laboratories employing radioactive cortisone labeled with tritium yielded information concerning the metabolites of cortisone and the routes by which they are eliminated. Exact quantitative evaluation of the total metabolites in terms of the amount given was difficult because of errors inherent in the methods employed for the analysis of tritium in very crude extracts. Other studies with C14 labeled testosterone, estrone, estradiol, progesterone, and desoxycorticosterone have been reported, and in general, these experiments showed a rapid elimination of the hormonal metabolites as conjugated substances in the urine (2). These analyses were possible 1This investigation was carried out under contract AT (30-1)-910 with the United States Atomic Energy

The Physiological Disposition and Metabolic Fate of Cortisone in Man

“…Only a minor fraction of the steroid (about four per cent) was excreted into the gastrointestinal tract via the bile. Previous results obtained with hydrocortisone were similar (1,33,34). Studies with corticosterone have yielded similar results; however, slightly more is excreted through the bile and less via the urine (8,35).…”

The desA and desB genes from Clostridium scindens ATCC 35704 encode steroid-17,20-desmolase

“…Prostate tissue contains 11β-hydroxyandrogens despite inhibition of host enzymes involved in synthesizing androgens (chemical castration) [27,28]. The role of 11β-OHAD formation by the gut microbiota in androgen accumulation in the prostate is unknown; however, we discovered that bacteria isolated from urine also express the bacterial steroid-17,20-desmolase pathway [11], and the majority of cortisol excretion from the body is via the urine [24,25]. Of note, we recently reported identification of the steroid-17,20-desmolase gene cluster in the genomes of urinary bacterial isolates and confirmed steroid-17,20-desmolase activity in an isolate of Propionimicrobium lymphophylum [11].…”

“…Extrapolations from radiometric studies in non-human primates (24) and data from humans (25) suggest that 15% of the 15 mg of cortisol are detected in the gut. Based on these studies, the concentration of cortisol metabolites in the ~0.4L human colon (26) downstream 5α-, 17β-reduced metabolites, are now thought to play an important role in activation of androgen receptor (27,28).…”

Studies on Phenolic Steroids in Human Subjects. II. The Metabolic Fate and Hepato-Biliary-Enteric Circulation of C14-Estrone and C14-Estradiol in Women1

“…Similar observations were made by Beer and Gallagher (17,18). Thus, following C14-labelled cortisol (27)(28)(29), testosterone (25,26), 1 1,8-hydroxyandrostenedione (31,36) or corticosterone (30) administration, over one-third of the radioactivity is excreted in the urine in the first four hours and over 60 to 70 per cent in the first 12 hours. On the other hand, following C14-estrone or C"-estradiol administration, only 12 per cent are excreted in the first four hours and about 33 per cent after 12 hours.…”