合成Luteinizing Hormone-Releasing Hormone (LH-RH) の代謝に関する研究

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The metabolism of 125I-LH-RH was studied in female, male and pregnant rats after an intravenous injection of the drug. The female rats received intravenous doses of 0.6 or 6 μg/kg of the drug (hereafter referred to as 0.6 μg/kg female group and 6 μg/kg female group, respectively). The male and pregnant rats both received the intravenous dose of 6 μg/kg of the drug (hereafter referred to as 6 μg/kg male group and 6 μg/kg pregnant group, respectively). After the intravenous injection, the animals were placed in metabolic cages and sacrificed periodically in order to obtain samples of blood, tissue and urine. The blood and tissue levels of the drug were determined by measuring the radioactivity in the blood and tissues. In addition, whole body autoradiography was also carried out in order to elucidate tissue distribution of the radioactivity in the body. Urinary excretion rates of the drug were determined by measuring the radioactivity in the urine. The radioactivity was measured by a well-type scintillation counter. Determination of plasma and urinary metabolites was performed by means of thin layer chromatography. The blood levels in the female and male groups showed biphasic patterns in which biological half lives in the first phase were about 7 to 10 minutes, thus suggesting that 125I-LH-R11 is rapidly metabolized and eliminated from the circulating blood. The plasma LH level in the 6 μg/kg female group increased higher than the control level 30 minutes later and reached a maximum (446 ng/ml) 60 minutes later. The tissue levels in the 0.6 μg/kg female group were high in the order of the thyroid gland, kidney, blood, uterus, ovary, lung, pancreas, hypophysis, liver, adrenal gland, spleen, skeletal muscle, adipose tissue and brain. The uptake of the radioactivity into the hypophysis was not specific and its level was similar to that of the pancreas. The tissue distribution in the 6 μg/kg female, male and pregnant groups showed similar patterns as those in the 0.6 μg/kg female group. On the basis of these results, it was concluded that no difference in the distribution patterns due to dosage, sex or pregnancy is clearly found. The uptake of the radioactivity into the fetus on the 21st day of gestation was considerably high and the same level as that of the placenta. The drug and its metabolites were mainly excreted into the urine and their excretion rates in the female and male groups were about 18 percent of the injected dose within 60 minutes and increased gradually with time. The results with respect to the plasma metabolites in all groups indicated that 125I-LH-RH injected intravenously is rapidly metabolized, since the unchanged 125I-LH-RH possibly occupies 50 percent of the total metabolites 10 minutes later. The metabolites in the fetal plasma and homogenate consisted of the possibly unchanged form having the same Rf value as that of authentic LH-RH, inorganic iodide, unidentified metabolites. This suggests that a minor part of the 125I-LH-RH injected intravenously may be transferred through the placenta into the fetus. Urinary metabolites in all groups, inorganic iodide and unidentified metabolites existed in the 30 minute urine samples and the excretion rate of inorganic iodide increased with time.
日本内分泌学会の論文

合成Luteinizing Hormone-Releasing Hormone (LH-RH) の代謝に関する研究

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