THE SECRETION, INTERCONVERSION AND CATABOLISM OF CORTISOL, CORTISONE AND SOME OF THEIR METABOLITES IN MAN

Abstract

ABSTRACT Trace doses of one or more of the following radioactive steroids were given to 2 normal and 4 rheumatoid arthritic men: cortisol, cortisone, 20α-dihydrocortisol, 20β-dihydrocortisol and tetrahydrocortisol. The specific activities of the given steroids and some of their unconjugated and conjugated metabolites in urine were measured. The secretion rates of cortisol and cortisone for the 2 normal men, deduced from their specific activities in urine, were found to be approximately equal and in sum approximately equal to the secretion rate of cortisol deduced from the specific activities of their conjugated metabolites. Evidence of the speed of interconversion of cortisol and cortisone was obtained by giving [4-14C] cortisol and [1,2-3H] cortisone simultaneously to the 2 normal subjects and measuring the specific activities of the cortisol and cortisone in urine; also by measuring, in one subject, the proportion of 14C and 3H in plasma cortisol and cortisone at intervals after administration. The specific activities were similar, the plasma cortisone was approximately 50 % derived from cortisol at 30 min and the plasma cortisol 40 % derived from cortisone at 40 min. For both the normal subjects given 14C-cortisol and 3H-cortisone the specific activities of the urinary unconjugated metabolites were consistently and markedly higher than those of the hydrolysed conjugated metabolites. The combined secretion rate of 20α- and 20β-dihydrocortisol and tetrahydrocortisol, for one normal subject, was estimated to be approximately 4 mg/24 h. It is suggested that the findings are consistent with the hypotheses that under basal unstressed conditions, 1, cortisol and cortisone are secreted by the adrenal in approximately equal amount; 2, cortisol and cortisone are interconverted at a speed that precludes the liver from being the main site of the interconversion; 3, the major fractions of the unconjugated and conjugated cortisol and cortisone metabolites are formed at different sites.