Studies on phenolic studies in human subjects. XX. In vivo conjugation and metabolism of estradiol-17beta in the human kidney.

Labeled estradiol-17beta (E2) was injected into one of the renal arteries of two human subjects. At the same time, an equimolar amount of differently labeled E2 was injected into a peripheral vein. The urinary metabolites were analyzed by DEAE-Sephadex A-25 column chromatography, countercurrent distribution (CCD) and enzyme hydrolyses. Identification was made by statistical analysis of data from CCD, thin layer chromatography (TLC) and co-crystallization upon admixture with authentic compounds. The major urinary metabolites were E2-17glucosiduronate (E2-17G), E2-3G and estriol-16G (E3-16G). The E2-17G was excreted immediately following injection of 14C-E2 into the renal artery of subject no. 1, at a rate which decreased gradually with time; whereas 3H-E2-17G did not appear in the urine until 5 min after injection of 3H-E2 into a peripheral vein. The excretion of 14C-E2-17G was very prominent as opposed to that of 3H-E2-17G; however, the excretion of both 14C- and 3H-E2-17G terminated within 30 min. 14C-E2-3G was excreted immediately following injection, whereas 3H-E2-3G did not appear until 5 min after the injection. Also, the excretion of 14C-E2-3G was more prominent as opposed to that of 3H-E2-3G. The excretion of these compounds was rapid in the initial 15 min after injection and then continued slowly for 1 h. On the other hand, 14C- and 3H-E2-16G appeared at 30 min after injection and the 3H/14C ratio was almost the same as that of the injected compounds. When subject no.2 was injected with the labeles reversed, the results were very similar to those described above. The results indicate that E2 is conjugated directly in the human kidney to form the 17G and 3G and excreted into the urine, whereas the conversion of E2 to E3 occurs systematically rather than in the kidney. In contrast of E3, the kidney appears to play a minor role (no more than 10% of the total E2 is involved) in the conjugation and/or metabolism of E2 in the human.