Metabolic transformation of hydrocortisone-4-C14 in normal men.

The fate of hydrocortisone in man has been extensively studied (l-7) but the quantitative aspects of the transformation to its many metabolites in individual normal subjects leave much to be desired (8-16). This study reports the metabolism of an intravenous dose of hydrocortisone-4-Cl4 in five normal male subjects and of an oral dose in one of these subjects. The metabolites” cortol, /I-cortol, cortolone, fl-cortolone, THE, THF, and ATF, HO-E, 11-OE, and HO-A-have been studied in five subjects by reverse isotope dilution and paper chromatography. The 5cu-H epimers of the cortols and cortolones were recently synthesized (17). They have been named allocortol (allopregnane-3a, llfi ,17a!, 2Ocr, 21-pentol) and allocortolone (llketoallopregnane-3cr, 17~ ,20a ,21-tetrol) and their 20&hydroxy epimers, /3-allocortol and /%allocortolone, respectively. The transformation of hydrocortisone-4-Cl4 to these 5~H steroids has been studied in one subject, and their isolation after a large dose of nonisotopic cortisone is reported. The radioactive studies afford a more precise knowledge of the quantitative relationships than hitherto available and, more important perhaps, establish the validity of methods by means of which information on these problems may be readily obtained. The results furnish further a basis for comparison of hydrocrotisone metabolism in the normal man with that found in different abnormal or pathological conditions.