Renal capture and oxidation of cortisol in man

Cortisol labeled at C-4 with ¹⁴C and in the α-position at C-ll with ³H was given iv to 3 subjects. Blood samples were obtained from arm vein, radial artery and renal vein at short time intervals. These were analyzed for cortisol, cortisone and tritiated water. Urine samples at frequent intervals were analyzed for cortisol, cortisone and tritiated water. The biological half-lives of the ¹⁴C and ³H species of cortisol, were, respectively, 60-75 and 30-45 min. The difference is the result of reduction of cortisone to cortisol. ³H appeared rapidly in water and approximately 50 % of the injected label was in the body water at the end of 2 hr. Measurements of the renal V-A differences in tritium water content indicated that about 10% of the ³H that eventually entered body water was the result of oxidation of cortisol by kidney llα-hydroxysteroid dehydrogenase. The isotope ratio ³H/¹⁴C of plasma cortisol was greater than that injected during the early samples, indicative of a large primary isotope effect reflecting the relatively impeded biochemical reactivity of the molecules with ³H on the α-face of C-ll. In the kidney, this was manifested by the fact that renal extraction of ³H-cortisol was only 2/3 as great as the extraction of ¹⁴C-cortisol. This difference was so large as to suggest strongly that ll(3-hydroxysteroid dehydrogenase may be the cellular capture mechanism for cortisol.