DIFFERENT EFFECTS OF INTERMITTENT AND CONTINUOUS GROWTH-HORMONE (GH) ADMINISTRATION ON SERUM SOMATOMEDIN-C INSULIN-LIKE GROWTH FACTOR-I AND LIVER GH RECEPTORS IN HYPOPHYSECTOMIZED RATS

DIFFERENT EFFECTS OF INTERMITTENT AND CONTINUOUS GROWTH-HORMONE (GH) ADMINISTRATION ON SERUM SOMATOMEDIN-C INSULIN-LIKE GROWTH FACTOR-I AND LIVER GH RECEPTORS IN HYPOPHYSECTOMIZED RATS
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DOI:
10.1210/endo-123-2-1053
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发表时间:
1988-08-01
期刊:
影响因子:
4.8
通讯作者:
KETELSLEGERS, JM
KETELSLEGERS, JM
中科院分区:
医学2区
文献类型:
--
作者:
MAITER, D;UNDERWOOD, LE;KETELSLEGERS, JM

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为了确定生长激素的传递方式是否对调节血清生长激素-G/胰岛素样生长因子I(Sm-C/IGF-I)和肝脏促生长激素受体(Sm-C/IGF-I)很重要,我们测量了去垂体大鼠的血清Sm-C/IGF-I浓度以及游离(H2O处理的匀浆)和总的(MgCl2处理的匀浆)肝脏GH结合部位,用大鼠(RGH)处理7天,连续给药(50和250微克/天)或间歇(4次皮下注射12.5微克/天)。在每日剂量为50微克时,间歇性RGH产生更大的体重增加[+29.7。+-]。0.8克(平均+-Se)]高于GH持续输注(23.3.+-)。2.0g;P<0.01)。同样,血清Sm/C/IGF-I浓度随着间歇性(0.33±-)的增加而升高。0.1U/ml),低于连续给药(0.17±-)。0.01U/ml;P<0.01)。反复注射生长激素所达到的血清Sm-C/IGF-I水平甚至高于连续注射高5倍的生长激素剂量(250微克/天;0.27±-)。0.02U/ml;P<0.05)。每天持续输注50和250微克的RGH使肝脏总生长激素受体的数量比对照组增加2.5倍。而频繁注射生长激素对生长激素结合无影响,血清Sm-C/IGFI浓度与肝脏生长激素结合部位无相关性(r=0.189;P=NS)。连续给药时,肝脏PRL受体的诱导率是间断给药时的10倍。在所有GH处理的大鼠中观察到的生长激素和催乳素结合位点之间的密切相关性(r=0.955;P<0.001)表明它们的调节可能是联系在一起的。这些结果表明,控制Sm-C/IGF-I产生和生长的调节机制可能不同于调节GH受体浓度的机制,GH脉冲对最大限度地刺激Sm/C-IGF和生长至关重要,但持续暴露GH则需要上调肝脏GH受体。
To determine if the pattern of GH delivery is important for the regulation of serum somatomedin-G/insulin-like growth factor I (Sm-C/IGF-I) and liver somatogenic receptors, we have measured serum Sm-C/IGF-I concentrations and free (H2O-treated homogenates) and total (MgCl2-treated homogenates) liver GH-binding sites in hypophysectomized rats treated for 7 days with rat (rGH), given either continuously by osmotic minipumps (50 and 250 .mu.g/day) or intermittently (four sc injections of 12.5 .mu.g/day). At a daily dose of 50 .mu.g, intermittent rGH produced greater weight gain [+29.7 .+-. 0.8 g (mean .+-. SE)] than continuous GH infusion (23.3 .+-. 2.0 g; P < 0.01). Likewise, the serum Sm/C/IGF-I concentration rose more with intermittent (0.33 .+-. 0.1 U/ml) than with continuous delivery (0.17 .+-. 0.01 U/ml; P < 0.01). The serum Sm-C/IGF-I level achieved with repeated GH injections was even greater than that after continuous delivery of a 5-fold higher GH dose (250 .mu.g/day; 0.27 .+-. 0.02 U/ml; P < 0.05). Continuous infusions of 50 and 250 .mu.g rGH/day increased the number of liver total GH receptors by 2.5-fold over that of controls. In contrast, frequent GH injections did not effect GH-binding, and the serum Sm-C/IGF-I concentration did not correlate with liver GH-binding sites in the GH-injected rats (r = 0.189; P = NS). Induction of hepatic PRL receptors was 10-fold higher when GH was given continously than when it was given intermittently. The close correlation observed between GH- and PRL-binding sites in all GH-treated rats (r = 0.955; P < 0.001) suggests that their regulation may be linked. These data suggest that the regulatory mechanism controlling Sm-C/IGF-I production and growth might be different from those that regulate GH receptor concentrations, with GH pulses being crucial for the maximal stimulation of Sm/C-IGF and growth, but continuous exposure to GH being required for up-regulation of liver GH receptors.