Thyroid hormone and growth hormone interact to regulate insulin-like growth factor-I messenger ribonucleic acid and circulating levels in the rat.
Thyroid hormone and growth hormone interact to regulate insulin-like growth factor-I messenger ribonucleic acid and circulating levels in the rat.
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DOI：
10.1210/endo-125-6-2905
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发表时间：
1989-12
期刊：
影响因子：
4.8
通讯作者：
M. Wolf;S. Ingbar;A. Moses
中科院分区：
文献类型：
--
作者：
M. Wolf;S. Ingbar;A. Moses
甲状腺激素通过改变GH的分泌和作用来影响生长。GH通过调节胰岛素样生长因子-I（IGF-I）的合成和分泌来介导其作用。IGF-I是一种多效性生长因子，由许多组织合成并作用于许多组织以调节细胞复制和分化功能。我们研究了甲状腺激素的直接作用和甲状腺激素和GH对垂体切除（hypox）大鼠体内IGF-I合成和分泌的调节的联合作用。除正常同窝出生大鼠和低氧对照组外，所有大鼠均接受100 μ g氢化可的松/100 g BW，持续10天。通过特异性RIA（正常大鼠，1 U/ml）测定循环IGF-I，并通过北方印迹杂交与反义cRNA探针测定肝脏IGF-I mRNA。1)用hGH（75 μ g，ip，每日两次）处理10天的低氧大鼠增加了17 g BW，而正常同窝出生的大鼠增加了70 g。GH显著增加肝脏IGF-I mRNA和循环IGF-I（末次GH注射后12 h为0.52 +/- 0.14 U/ml，低氧对照组为0.03 +/- 0.02）。2)T4（1 μ g/100 g BW，ip）给药10天既不增加体重，也不增加肝脏IGF-I mRNA，也不增加循环IGF-I。3)大鼠接受T4处理10天，然后单次注射1 mg GH，ip，肝脏IGF-I mRNA和循环IGF-I水平升高，与接受急性GH单独给药的大鼠相同（IGF-I，12 h，0.31 +/- 0.09 vs. 0.36 +/- 0.06 U/ml）。4)单次注射T3（1.5 μ g/100 g BW，ip）处理的低氧大鼠肝脏IGF-I mRNA略有增加，但循环IGF-I水平无显著变化。5)对低氧大鼠单次注射T3 + GH使IGF-I mRNA水平高于单独注射GH的大鼠，并使血清IGF-I水平升高至0.48 +/- 0.12 U/ml，而单独注射GH为0.36 +/- 0.06 U/ml。6)GH治疗10天后，单次注射T3降低了肝脏IGF-I mRNA和循环IGF-I（0.52 +/- 0.14至0.16 +/- 0.06 U/ml，T3后6 h）。这些研究表明，甲状腺激素对IGF-I合成的直接影响相对较小，但对GH刺激的IGF-I合成和分泌有重要影响。这些影响的模式取决于垂体的完整性，肝脏先前暴露于GH和/或甲状腺激素，以及GH和甲状腺激素给药之间的时间关系。
Thyroid hormones influence growth in part by altering the secretion and effects of GH. GH, in turn, mediates its effects by regulating the synthesis and secretion of insulin-like growth factor-I (IGF-I). IGF-I is a pleiotropic growth factor that is synthesized by many tissues and acts on many tissues to regulate both cellular replication and differentiated function. We have studied the direct effects of thyroid hormones and the combined effects of thyroid hormones and GH on the regulation of IGF-I synthesis and secretion in hypophysectomized (hypox) rats in vivo. All rats, except normal littermates and a hypox control group, received 100 micrograms hydrocortisone/100 g BW for 10 days. Circulating IGF-I was measured by specific RIA (normal rats, 1 U/ml), and hepatic IGF-I mRNA was measured by Northern blot hybridization with an antisense cRNA probe. 1) Hypox rats treated with hGH (75 micrograms, ip, twice daily) for 10 days gained 17 g BW vs. 70 g for normal littermates. GH markedly increased hepatic IGF-I mRNA and circulating IGF-I (0.52 +/- 0.14 U/ml 12 h after the last GH injection vs. 0.03 +/- 0.02 for hypox controls). 2) T4 (1 micrograms/100 g BW, ip) for 10 days increased neither weight, hepatic IGF-I mRNA, nor circulating IGF-I. 3) Rats treated with T4 for 10 days followed by a single injection of 1 mg GH, ip, increased hepatic IGF-I mRNA and circulating IGF-I levels comparably as in rats receiving acute GH alone (IGF-I, 12 h, 0.31 +/- 0.09 vs. 0.36 +/- 0.06 U/ml). 4) Hypox rats treated with a single injection of T3 (1.5 micrograms/100 g BW, ip) had slightly increased hepatic IGF-I mRNA, but showed no significant change in circulating IGF-I levels. 5) A single injection of T3 plus GH to hypox rats increased IGF-I mRNA levels above those in rats injected with GH alone and increased serum IGF-I levels to 0.48 +/- 0.12 U/ml compared to 0.36 +/- 0.06 U/ml for GH alone. 6) After 10 days of GH treatment, a single injection of T3 lowered both hepatic IGF-I mRNA and circulating IGF-I (0.52 +/- 0.14 to 0.16 +/- 0.06 U/ml, 6 h after T3). These studies demonstrate that thyroid hormones have relatively little direct effect on IGF-I synthesis but can have major effects on GH-stimulated IGF-I synthesis and secretion. The pattern of these effects depends on the integrity of the pituitary gland, prior exposure of the liver to GH and/or thyroid hormones, and the temporal relationship between GH and thyroid hormone administration.