正常周期婦人に [Des-Gly<SUP>10</SUP>-NH<SUB>2</SUB>, Pro<SUP>9</SUP>-ethylamide] -LH-RHを投与した時の下垂体Gonadotropinの反応に関する研究
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This study was designed to investigate the pituitary responsiveness of normal, regularly menstruating women to [Des-Gly<SUP>10</SUP>-NH<SUB>2</SUB>, Pro<SUP>9</SUP>-ethylamide] -LH-RH, the first superpotent analog of LH-RH. Also in this study, the LH-RH/FSH-RH activity of [Des-Gly<SUP>10</SUP>-NH<SUB>2</SUB>, Pro<SUP>9</SUP>-ethylamide] -LH-RH was compared with that of synthetic LH-RH in the follicular phase, and the half-life value of the analog in the blood was calculated.<BR>[Des-Gly<SUP>10</SUP>-NH<SUB>2</SUB>, Pro<SUP>9</SUP>-ethylamide] -LH-RH was given subcutaneously in a dose of 100μg to 17 women during different phases of the menstrual cycle. Five subjects were studied in the follicular phase (days 5, -6); 7 subjects were studied in the preovulatory phase (1-3 days before the expected date of ovulation); and the remaining 5 subjects were studied in the luteal phase (5-6 days after the BBT elevation). Five other subjects were given 100μg of synthetic LH-RH subcutaneously in the follicular phase (days 5-6) for a comparison. Blood samples were obtained under a prearranged schedule before and after the injection. The plasma levels of LH, FSH, estradiol-17β and progesterone were determined by radioimmunoassay. The gonadotropin response during the 6-hr period after the injection was assessed for Student's t-test and significant correlation with basal gonadal steroid levels using Pearson's correlation coefficient.<BR>Unexpected changes in the gonadotropin response were observed in 2 subjects studied during the preovulatory phase : the plasma level of LH in these 2 subjects continued to increase gradually after the injection and reached its peak 48 and 120 hours later, and the peak levels of LH were 295 and 313 mIU/ml, respectively. The response pattern of FSH was almost similar to that of LH. Such a large amount of gonadotropin release could have been due to the action of the endogenous LH-RH at midcycle as well as the depot effect of the analog. The plasma level of estradiol-17β in these 2 subjects also increased slowly after the injection and reached its peak 24 hours before their respective LH peaks, and then decreased abruptly on the following day. These 2 subjects were excluded from the following statistical analyses.<BR>The LH response to 100μg of the analog was significantly greater in both the preovulatory phase and the luteal phase than in the follicular phase (P<0.01 and P<0.05, respectively). There was no significant difference in the LH response between the preovulatory and luteal phases. The plasma level of LH reached its peak 2-3 hours after the subcutaneous injection of the analog in most of the subjects. The peak levels of LH (mean ± SE) were 101.4 ± 17.2 mIU/ml in the follicular phase, 280.3 ± 31.1 mIU/ml in the preovulatory phase, and 172.6 ± 31.3 mIU/ml in the luteal phase. The mean plasma levels of LH 6 hours after the injection in the follicular and luteal phases were still significantly elevated (P<0.02 and P<0.05, respectively), and they were 4.3 and 7.8 times the preinjection levels, respectively. There was no significant difference in the FSH response to the analog between the three different phases. The plasma level of FSH reached its peak 2-4 hours after the subcutaneous injection of the analog in most of the subjects. The peak levels of FSH (mean ± SE) were 22.4 ± 3.6 mIU/ml in the follicular phase, 57.8 ± 17.7 mIU/ml in the preovulatory phase, and 20.9 ± 4.0 mIU/ml in the luteal phase. The mean plasma levels of FSH 6 hours after the injection in the follicular and luteal phases were still significantly elevated (P<0.01 and P<0.05, respectively), and they were 2.4 and 2.9 times the preinjection levels, respectively.
- 日本内分泌学会の論文
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