INTRAVENOUS GROWTH HORMONE GROWTH RESPONSES TO PATTERNED INFUSIONS IN HYPOPHYSECTOMIZED RATS

INTRAVENOUS GROWTH HORMONE GROWTH RESPONSES TO PATTERNED INFUSIONS IN HYPOPHYSECTOMIZED RATS
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DOI:
10.1677/joe.0.1040053
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发表时间:
1985-01-01
影响因子:
4
通讯作者:
ROBINSON I C A F
ROBINSON I C A F
中科院分区:
医学2区
文献类型:
--
作者:
CLARK R G;JANSSON J-O;ROBINSON I C A F

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将切除垂体的幼龄大鼠长期留置静脉内插管,通过旋转连接到多通道泵送系统,以连续或脉冲方式输送GH [生长激素]数天。连续静脉输注人GH 5天,体重和尾长呈剂量依赖性增加,而不增加摄食量。通过s.c.或静脉注射途径显示直接静脉注射途径的有效性是3倍。以2种剂量(12或36 mU/天,8次脉冲/天,5分钟持续时间,每3小时一次)脉冲式静脉输注人或牛GH比以相同日剂量连续静脉输注GH产生更大的体重增加。连续输注牛GH在连续2个5天给药期的第2个中产生较低的生长速率;对脉冲GH的反应未随时间减弱。体重增加和长骨生长均受到GH脉冲频率的影响; 9脉冲/天比3脉冲/天更有效,而3脉冲/天又比1脉冲/天产生更大的生长反应。保持GH脉冲频率恒定和不同的脉冲持续时间(4,16或64分钟)没有影响生长速率。GH的长期脉冲静脉输注模拟内源性分泌模式,并且当以生理学上适当的脉冲频率给予时最有效。
Young hypophysectomized rats were maintained with chronic indwelling i.v. cannulae attached via swivels to a multichannel pumping system programmed to deliver GH [growth hormone] in a continuous or pulsatile pattern for several days. Continuous i.v. infusions of human GH for 5 days produced dose-dependent increases in body wt and tail length, without increasing food intake. A comparison of GH infusions by the s.c. or i.v. route showed that the direct i.v. route was 3-fold more effective. Pulsatile i.v. infusions of human or bovine GH at 2 doses (12 or 36 mU/day, eight pulses/day, 5 min duration, every 3 h) produced greater increases in body weight than continuous i.v. infusions of GH at the same daily dose. Continuous infusions of bovine GH produced a lower growth rate in the 2nd of 2 consecutive 5 day treatment periods; the responses to pulsatile GH did not diminish with time. Both body wt gain and long-bone growth were affected by the frequency of GH pulses; 9 pulses/day were more effective than 3 pulses/day which in turn produced larger growth responses than 1 pulse/day. Keeping GH pulse frequency constant and varying pulse duration (4, 16 or 64 min) did not affect growth rates. Long-term pulsatile i.v. infusions of GH mimic the endogenous secretory pattern, and are most effective when given at the physiologically appropriate pulse frequency.