In vivo and in vitro conjugation and metabolism of estrogens by the baboon kidney.

Labeled estrogen was injected into one of the renal arteries of baboons and urine was collected separately from each ureter via ureterostomy at various time intervals over a period of 7 h; the urinary metabolites were analyzed by DEAE-Sephadex chromatography and enzyme hydrolyses. Identification of the aglycones was made by TLC and co-crystallization upon admixture with authentic compounds. When [3H]estradiol-17beta (E2) was injected into one of the renal arteries, the major metabolites were [3H]E2-3-glucosiduronate (E2-3G) and [3H]estrone-3-glucosiduronate (E1-3G); [3H]E2-3G was excreted predominantly into the urine from the injected side during the initial 30 min after injection. Formation of [3H]E1-3G was not detectable for the first 5 min in the urine from either side. However, its excretion gradually increased and the amount was almost equal from both sides in the later hours of collection. Injection of [3H]E1 revealed ready conjugation (as E1-3G) by the kidney without significant reduction at position-17. When E2-3G, labeled with 3H at positions 6,7 and with 14C in the glucuronic moiety, was injected, it was quickly excreted in the urine of the injected side. The ratio of 3H/14C of E2-3G excreted in the urine was the same as that of the injected E2-3G. In the later periods, E1-3G, which had a slightly increased 3H/14C ratio, appeared in the urine. These results indicate that E2 and E1 are conjugated directly in the kidney to form the 3G which is excreted into the urine and that effective dehydrogenation or reduction of the steroids in vivo does not take place in the kidney. The results also show that conjugated E2 (E2-3G) is quickly excreted by the kidney of the baboon without any change in its form and that the E2-3G is dehydrogenated to E1-3G during its general circulation without significant prior removal of the glucuronic moiety. When [3H]estriol (E3) was injected, facile glucuronidation to E3-16G by the kidney was shown. Injection of an equimolar mixture of [14C]E3 and [3H]E2 showed rapid excretion of [14C]E3-16G as opposed to the slower excretion of [3H]E2-3G. These results suggested that the active sites of these conjugating enzyme systems in the kidney may be different.