Acute down-regulation of the somatogenic receptors in rat liver by a single injection of growth hormone.
Acute down-regulation of the somatogenic receptors in rat liver by a single injection of growth hormone.
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DOI：
10.1210/endo-122-4-1291
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发表时间：
1988-04
期刊：
影响因子：
4.8
通讯作者：
D. Maiter;L. Underwood;M. Maes;J. Ketelslegers
中科院分区：
文献类型：
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作者：
D. Maiter;L. Underwood;M. Maes;J. Ketelslegers
长时间连续施用 GH 会诱导大鼠肝脏中的体源性受体。然而，由于 GH 分泌是脉动的，并且血清 GH 浓度的急剧变化对肝脏 GH 受体的影响尚不清楚，因此我们测量了单次皮下注射大鼠 GH（100 微克/100 g BW；n = 29）后 1 至 24 小时内处死的垂体切除（hypox）大鼠肝脏中的总 GH 结合位点（MgCl2 处理的匀浆）和游离（水处理的匀浆）GH 结合位点。注射媒介物后立即或 3 小时对对照缺氧大鼠 (n = 10) 进行研究。 GH 注射导致肝脏 GH 受体总数和游离 GH 受体显着减少，但这些变化遵循不同的动力学模式。游离受体迅速下降（降至对照的 17%），与血清中最大 GH 浓度同时（1 小时）达到最低点。这些游离受体随后增加，在 GH 注射后 12 小时恢复正常。相反，总 GH 受体在 1 小时时略有增加，在 6 小时时降至最低值（对照的 53%），并在 12 小时时恢复正常。血清免疫反应性生长调节素-C/胰岛素样生长因子 I 浓度在 GH 注射后 12 小时达到峰值。对缺氧大鼠中的总肝脏 GH 受体和游离肝脏 GH 受体进行定量，这些大鼠在 3 小时前注射了剂量为 2.5-500 微克/100 g BW 的大鼠 GH 或载体。总结合位点和游离结合位点均以剂量依赖性方式减少；最大反应分别比对照值低 40% 和 90%。当给予 10 微克 GH/100 g BW 时，GH 结合达到半最大减少。这些数据表明，血清中 GH 的激增导致肝脏体细胞结合位点的时间和剂量依赖性下调，并且与配体诱导的受体内化和降解一致。
Prolonged continuous administration of GH induces somatogenic receptors in rat liver. However, because GH secretion is pulsatile and the effect of acute changes in serum GH concentrations on liver GH receptors is unknown, we measured total (MgCl2-treated homogenates) and free (water-treated homogenates) GH-binding sites in the livers of hypophysectomized (hypox) rats killed between 1 and 24 h after a single sc injection of rat GH (100 micrograms/100 g BW; n = 29). Control hypox rats (n = 10) were studied immediately or 3 h after injection of vehicle. GH injection caused profound decreases in both total and free liver GH receptors, but these changes followed different kinetic patterns. Free receptors declined rapidly (to 17% of control), reaching a nadir at the same time (1 h) as the maximal GH concentration in serum. These free receptors then increased, returning to normal 12 h after GH injection. In contrast, total GH receptors were slightly increased at 1 h, decreased to their minimal value at 6 h (53% of control), and returned to normal at 12 h. Serum immunoreactive somatomedin-C/insulin-like growth factor I concentrations peaked 12 h after GH injection. Total and free liver GH receptors were quantitated in hypox rats that had been injected 3 h previously with doses of rat GH from 2.5-500 micrograms/100 g BW or with vehicle. Both total and free binding sites decreased in a dose-dependent manner; the maximal responses were 40% and 90% below control values, respectively. Half-maximal reductions in GH binding were achieved when 10 micrograms GH/100 g BW were given. These data suggest that a surge of GH in serum leads to a time- and dose-dependent down-regulation of the liver somatogenic binding sites and are consistent with ligand-induced internalization and degradation of the receptor.