エストロゲンの抱合と代謝:II. in vivo, 犬腎におけるestroneの抱合と代謝

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Labeled estrone (E1) or conjugated E1 was injected into one of the renal arteries of dogs, and urine was collected separately from each ureter via ureterostomy at various time intervals over a period of 7h. In some cases, the differently labeled E1 or conjugated E1 was injected into a peripheral vein simultaneously with the injection into a renal artery. The urinary metabolites were analyzed by DEAE Sephadex A-25 column chromatography, Amberlite XAD-2 resin column chromatography and enzyme hydrolysis. Identification of aglycones were made by TLC. Non-labeled metabolites were analyzed with GC-mass spectrometry. When [6, 7-3H] E1 was injected into one of the renal arteries and [4-14C] E1 was injected into a peripheral vein simultaneously, the cumulative excretion of3H in the urine from both sides was 1.6%, and that of 14C was 14.2% in 7h. (Fig. 1) 3H was excreted equally from both kidneys similar to 14C. 14C labeled metabolites were excreted about nine times greater than 3H labeled metabolites. Formation of glucosiduronate was not detectable in the early period (Fig. 2), but appeared in the late period. (Fig. 3) The major metabolites in the urine of the late period were identified as E 1-glucosiduronate (E 1-G), estradiol-17α-G (E2 -17α-G), E2-17β-G, keto E2 -17β-G, methoxy E1 -G, E1-sulfate (E1-S), E2-17α-S and E2-17β-S. These results show that E1 is not conjugated in the dog kidney primary but conjugated and metabolized during general circulation and excreted in the urine in the late interval. When [4-14C] E1 was injected into one of the renal arteries and [6, 7-3H] E1 was injected into a peripheral vein, the cumulative excretion of 3H in the urine from both sides was 2.0%, and that of 14 C was 15.9% in 7h. (Fig. 4) Here also 14C was excreted equally from both kidneys similar to 3 H. Following the injection of [2, 4, 6, 7-3H] E1 and [4-14C] E1 into one of the renal arteries, the cumulative excretion of 3 H was 18.6%, and 14C was 13.7% in the urine from both sides. (Fig. 5) In this experiment using [2, 4, 6, 7-3H] E1, the amount of excreted3 H was also the same as that of 14C. These results show that some metabolism at the 6, 7 position of E1 occurs during the general circulation. When [6, 7-3H] E1-S and [4-14C] E1 were injected into one of the renal arteries, 3H was rapidly excreted in the injected-side urine in the early period. (Fig. 7) Large amounts of [6, 7-3H] E1-S and 3H labeled glucosiduronate were excreted in the urine from the injected-side kidney in the initial 10 min. following the injection. (Fig. 8) The analysis of the metabolites in the early interval showed that 3H-E1-S was converted to 3H-E1-G and 3H-E2-S in small amounts in the kidney. In the experiment with the injection of [6, 7-3 H] E1-G into one of the renal arteries and [4-14C] E1 into a peripheral vein, the most rapid excretion of 3 H-E1-G through the kidney was shown. (Fig. 9)
日本内分泌学会の論文

エストロゲンの抱合と代謝:II. in vivo, 犬腎におけるestroneの抱合と代謝

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