METABOLISM OF 4-C<sup>14</sup>-CORTISOL IN MAN: BODY DISTRIBUTION AND RATES OF CONJUGATION*†

Ha, Decker; Cj, Migeon; Ac, Paul; Lt, Samuels; Aa, Sandberg; Df, Smith

doi:10.1210/jcem-16-9-1137b

Cited by 91 publications

(35 citation statements)

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“…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).…”

Section: Discussionsupporting

confidence: 53%

The Physiological Disposition and Metabolic Fate of Cortisone in Man

Peterson¹,

Pierce²,

Wyngaarden³

et al. 1957

J. Clin. Invest.

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In an earlier paper we described studies on the physiological disposition and metabolic fate of hydrocortisone in man (1). This paper describes similar studies on cortisone. Although contributing very little to the body pool of adrenal cortical steroids, cortisone has been used extensively as a therapeutic agent, and it was therefore of interest to compare its metabolism with that of hydrocortisone. Large doses of cortisone and hydrocortisone were administered intravenously and rates of disappearance from the plasma determined in normal subjects and in patients with liver disease, myxedema, thyrotoxicosis, and rheumatoid arthritis. Trace quantities of cortisone-4-C" and hydrocortisone-4-C" were employed in certain studies. From these studies, information was obtained regarding rate of metabolic transformation, rate of absorption, rates and routes of excretion of cortisone and its metabolites, and, to some extent, the identity and amount of these metabolites. Information was also obtained on the in vivo conversion of cortisone to hydrocortisone. MATERIALS AND METHODSAdministration of steroid. The steroids were dissolved in 25 ml. ethanol and added to 500 ml. of sterile five per cent dextrose in water. This solution was administered intravenously over a period of 10 to 20 minutes. For oral or intramuscular administration the steroids were suspended in saline. Cortisone-4-C" was administered intravenously in trace quantities in a small volume of five per cent ethanol in water over a period of 3 to 5 minutes, or mixed with carrier cortisone and given in 500 ml. of three per cent ethanol in five per cent dextrose in sterile distilled water. Following the administration of the steroids, blood samples were drawn in heparinized syringes every 20 or 30 minutes for 2 hours-or more.Urine samples were collected and preserved by freezing.Methods of assay. The extraction procedures for the steroids in plasma and urine were the same as those de-

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Section: Discussionsupporting

confidence: 53%

The Physiological Disposition and Metabolic Fate of Cortisone in Man

Peterson¹,

Pierce²,

Wyngaarden³

et al. 1957

J. Clin. Invest.

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“…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.…”

Section: ) Of Estrone and Estradiol Has Enlarged Ourcontrasting

confidence: 54%

“…Radioactive estrone or estradiol was cleared from the plasma rapidly and at somewhat faster rates than the free steroid clearance following the administration of C"4-cortisol or Cl(-testosterone (25,29). In addition, there was no significant difference in the clearance of the free steroids among the various subjects studied.…”

Section: ) Of Estrone and Estradiol Has Enlarged Ourmentioning

confidence: 85%

“…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.…”

Section: ) Of Estrone and Estradiol Has Enlarged Ourmentioning

confidence: 99%

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

Sandberg¹,

Slaunwhite²

1957

J. Clin. Invest.

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170

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“…It was thought that radioactive cortisol might be useful since it would permit a dynamic Preliminary study on newborn infants. If, following the injection of radioactive material to a mother, a large part of the dose were to cross the placenta, we had to be assured that the newborn would dispose of the compound as rapidly as do normal adults (10)(11)(12)(13). Therefore, in a first step of the present study, we measured the urinary excretion of radioactivity during the 48-hour period following the administration of a minimal dose of 4-C!-cortisol (1.5 X 1OV mticrocurie) to two newborns, 15 and Z2 hours of age.…”

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confidence: 99%