Tracer Studies of the Absorption and Fate of Steroid Hormones in Man 1

Abstract

The steroid hormones testosterone, hydrocortisone and corticosterone present certain paradoxical physiological problems in their transport and metabolism in the organism. Thus hydrocortisone is highly effective orally whereas testosterone has little biological activity when fed. Insofar as man and the rodent are concerned, there appears to be no appreciable species difference in the response to these two hormones when given by mouth. On the other hand, there is a striking difference in the manner in which these two species eliminate the end product of hormone metabolism (1-3) and, in addition, dissimilar compounds are formed and excreted by each. A further species difference exists in that hydrocortisone is the principal product of the adrenal secretion in man, whereas in the rat corticosterone appears to be the major component (4).Since an interpretation of these differences might give a deeper insight into the mechanism of hormonal action, an exploration of the problems implicit in these facts was undertaken. First the possibility was entertained that corticosterone might behave like a hormone "foreign" to the human and would, as a consequence, differ from the "normal" secretion, hydrocortisone, in either the rate or route of elimination of its metabolites. Second, cortisone acetate was compared with hydrocortisone and corticosterone to establish, by the same criteria, whether similar processes are operative with the biologically active ester as with the free hormones. Third, testosterone was given by both the oral and intravenous route in order to ' This investigation was carried out under contract AT30-1 910 with the United States Atomic Energy Commission and supported in part by a research grant (C-440) from the National Cancer Institute of the National Institutes of Health of the United States Public Health Service, and a research grant from the American Cancer Society.have a comparison of a chemically similar steroid hormone, differing in biological activity, with the two adrenal hormones. Fourth, the absorption of hydrocortisone and testosterone from the intestinal tract was studied in human subjects with the thoracic duct cannulated. Fifth, the importance of biliary excretion in the human was evaluated in patients with complete biliary fistulas. The results reported are of interest for the comparative physiology of the hormones since the findings obtained in other species can now be related to the sequence of events observed with the human. EXPERIMENTALThe subjects studied were patients in a metabolic ward. The pertinent clinical data concerning these patients are summarized in Table I. The three subjects with bile fistula, FBT-1, T-3, B-1, were studied in the interval between the two stages of an operative attempt to correct bile duct obstruction as the result of a tumor. In each case the fistula was deliberately established during the first operative procedure by complete diversion of bile flow to the exterior through an indwelling cannula. The completeness of the fistula was confirmed by the absence ...

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

“…Even though, in general, the importance of the biliary excretion of estrogens and their enterohepatic circulation had been accepted in the past to be true for animals, e.g., dogs, cows (6, 37), such has not been the case for human subjects. Our data demonstrate, however, that not only was more of the radioactivity of C4-estrone or C"-estradiol excreted in the bile than that seen following the injection of any other known steroid in human subjects (25,(28)(29)(30)38), but in addition more of the radioactivity appeared in the bile than in the urine of three of the bile-fistula subjects. This establishes the importance of biliary excretion in the metabolism of estrogens in women.…”

The Physiological Disposition and Metabolic Fate of Cortisone in Man

“…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).…”

Metabolism of Vitamin D3-3H in Human Subjects: Distribution in Blood, Bile, Feces, and Urine*

“…This latter assumption is tentative in view of reports wherein species differences in hepatic conjugation and biliary excretion of other steroids have been noted for man and rodents (29).…”