Wolf M, Ingbar S H, Moses A C
Department of Medicine, Charles A. Dana Research Institute, Boston, Massachusetts.
Endocrinology. 1989 Dec;125(6):2905-14. doi: 10.1210/endo-125-6-2905.
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.
甲状腺激素部分通过改变生长激素（GH）的分泌及其作用来影响生长。反过来，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。我们在体内研究了甲状腺激素的直接作用以及甲状腺激素与GH联合作用对垂体切除（hypox）大鼠IGF-I合成和分泌调节的影响。除正常同窝仔鼠和hypox对照组外，所有大鼠均接受100微克氢化可的松/100克体重，持续10天。通过特异性放射免疫分析（RIA）测定循环中的IGF-I（正常大鼠为1 U/ml），并通过与反义cRNA探针的Northern印迹杂交测定肝脏IGF-I mRNA。1）用hGH（75微克，腹腔注射，每日两次）治疗10天的hypox大鼠体重增加17克，而正常同窝仔鼠增加70克。GH显著增加肝脏IGF-I mRNA和循环中的IGF-I（最后一次GH注射后12小时为0.52±0.14 U/ml，而hypox对照组为0.03±0.02）。2）T4（1微克/100克体重，腹腔注射）10天既未增加体重、肝脏IGF-I mRNA，也未增加循环中的IGF-I。3）用T4治疗10天的大鼠随后单次腹腔注射1毫克GH，肝脏IGF-I mRNA和循环中的IGF-I水平与单独接受急性GH的大鼠相当（IGF-I，12小时时为0.31±0.09 vs. 0.36±0.06 U/ml）。4）单次腹腔注射T3（1.5微克/100克体重）的hypox大鼠肝脏IGF-I mRNA略有增加，但循环中的IGF-I水平无显著变化。5）对hypox大鼠单次注射T3加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和循环中的IGF-I（T3注射后6小时从0.52±0.14降至0.16±0.06 U/ml）。这些研究表明，甲状腺激素对IGF-I合成的直接作用相对较小，但对GH刺激的IGF-I合成和分泌可能有重大影响。这些作用的模式取决于垂体的完整性、肝脏先前对GH和/或甲状腺激素的暴露以及GH和甲状腺激素给药之间的时间关系。
