Estronesulfateの生体内動態とその意義
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It is well known that estrone sulfate (E<SUB>1</SUB>-S) is a major estrogen in human serum; however, the physiological role of E<SUB>1</SUB>-S is not yet clarified. In order to elucidate this physiological role, the following experiments were performed.<BR>1) The conjugation and metabolism of E<SUB>1</SUB>-S in the Japanese monkey (Macaca fuscata) <BR>Following an injection of the equimolar mixture of [4-<SUP>14</SUP>C] E<SUB>1</SUB> and [6, 7-<SUP>3</SUP> H] E<SUB>1</SUB> -S into a femoral vein of the Japanese monkeys, urine, blood (from a femoral artery) and bile were collected at various time intervals over a period of 2 hs. Various tissues, that is, kidney, liver, lung, endometrium, fatty tissue, myometrium and skin, were taken after sacrifice. The metabolites were analyzed by DEAE Sephadex A-25 column chromatography, enzyme hydrolysis and TLC. E<SUB>1</SUB>, E<SUB>1</SUB>-glucosiduronate (E<SUB>1</SUB>-G) and E<SUB>1</SUB>-S were identified in the serum, and E<SUB>1</SUB>, E<SUB>1</SUB>-G, estradiol-17α-3G (E<SUB>2</SUB>-17α-3G), estradiol-17β-3G (E<SUB>2</SUB> -3G), E<SUB>1</SUB> -S and E<SUB>2</SUB>-17α-S were identified as urinary metabolites. In the bile, 16α-hydroxy-estrone-G was also present. A large amount of [<SUP>3</SUP>H] E<SUB>1</SUB> -S was present in the early collection of the serum, and [<SUP>3</SUP>H] E1-G gradually increased later. <SUP>14</SUP>C, which was present less than 3 H in the serum was conjugated to [<SUP>14</SUP> C] E<SUB>1</SUB>-G and [<SUP>14</SUP> C]E<SUB>1</SUB> -S later. Namely, E<SUB>1</SUB> -S was one of the conjugated forms of E<SUB>1</SUB> in the serum. There was much <SUP>14</SUP>C and less <SUP>3</SUP>H in the lung tissue. Therefore, one of the physiological roles of E<SUB>1</SUB>-S is to pass through the pulmonary circulation as compared to E<SUB>1</SUB>. E<SUB>1</SUB> -S and E<SUB>1</SUB> were conjugated into E<SUB>1</SUB> -G and E<SUB>1</SUB> -S in the general circulation. Glucosiduronate of estrogens was mainly excreted into the urine.<BR>2) Renal conjugation and metabolism of E<SUP>1</SUP> and E<SUB>1</SUB>-S<BR>Following the injection of labelled estrogen into one of the renal arteries, urine was collected from both kidneys. Urinary metabolites were analyzed using the same methods as above.1 Injection of [4-<SUP>14</SUP>C] E<SUB>1</SUB> into one of the renal arteries and [6, 7-<SUP>3</SUP>H] E1 into a peripheral vein.<BR>A larger amount of [<SUP>14</SUP>C] E<SUB>1</SUB> -G was identified in the injected side urine in the early period (5-10 min) rather than [<SUP>3</SUP> H] E<SUB>1</SUB> -G. This denotes the formation of glucosiduronation in the kidney of the Japanese monkey in vivo.<BR>2 When [4-<SUP>14</SUP>C] E<SUB>1</SUB> and [6, 7-<SUP>3</SUP> F-<SUP>3</SUP>] E<SUB>1</SUB> -S were injected into one of the renal arteries of the monkey, El-S was partially filtered from the kidney directly, but no excretion of E<SUB>1</SUB> into the urine was detectable. It was shown that E<SUB>1</SUB>-S was hydrolyzed and then was conjugated into E<SUB>1</SUB> -G in the general circulation, and after a while the E<SUB>1</SUB> -G was filtered from the kidney.<BR>3 Following the injection of [4-<SUP>14</SUP>C] E<SUB>1</SUB> and [6, 7<SUP>3</SUP>H] E<SUB>1</SUB>-G into one of the renal arteries, E<SUB>1</SUB>-G was filtered very quickly from the kidney even compared to E<SUB>1</SUB>-S.<BR>3) Hydrolysis of E<SUB>1</SUB>-S in the endometrium<BR>The mixture of [6, 7<SUP>3</SUP> FI] E<SUB>1</SUB> -S and [4-<SUP>14</SUP>C] E<SUB>1</SUB> was incubated with human endometrium.<BR>The ethanol extract was analyzed by DEAE Sephadex A-25 column chromatography, enzyme hydrolysis and TLC. Myometrium, fatty tissue and muscle were also incubated as the control.<BR>The results were as follows : <BR>The hydrolysis of E<SUB>1</SUB> -S in the endometrium, target organ of estrogen, was 19.3% and those in the fatty tissue, muscle, and myometrium were 5.8, 3.3, 1.9% respectively.
- 日本内分泌学会の論文
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