Thomas M R, Miell J P, Taylor A M, Ross R J, Arnao J R, Jewitt D E, McGregor A M
Department of Cardiology, King's College Hospital, Denmark Hill, London, UK.
J Mol Endocrinol. 1993 Jun;10(3):313-23. doi: 10.1677/jme.0.0100313.
Thyroid hormones are essential for the normal growth and development of many tissues. In the rat, hypothyroidism is associated with growth impairment, and hyperthyroidism with the development of a hypercatabolic state and skeletal muscle wasting but, paradoxically, cardiac hypertrophy. The mechanism by which thyroid hormone produces cardiac hypertrophy and myosin isoenzyme changes remains unclear. The role of IGF-I, an anabolic hormone with both paracrine and endocrine actions, in producing cardiac hypertrophy was investigated during this study in hyperthyroid, hypothyroid and control rats. A treated hypothyroid group was also included in order to assess the effect of acute normalization of thyroid function. Body weight was significantly lower in the hyperthyroid (mean +/- S.E.M.; 535.5 +/- 24.9 g, P < 0.05), hypothyroid (245.3 +/- 9.8 g, P < 0.001) and treated hypothyroid (265.3 +/- 9.8 g, P < 0.001) animals when compared with controls (618.5 +/- 28.6 g). Heart weight/body weight ratios were, however, significantly increased in the hyperthyroid (2.74 +/- 0.11 x 10(-3), P < 0.01) and treated hypothyroid (2.87 +/- 0.07 x 10(-3), P < 0.001) animals when compared with controls (2.26 +/- 0.03 x 10(-3). Serum IGF-I concentrations were similar in the control and hyperthyroid rats (0.91 +/- 0.07 vs 0.78 +/- 0.04 U/ml, P = 0.26), but bioactivity was reduced by 70% in hyperthyroid serum, suggesting a circulating inhibitor of IGF. Serum IGF-I levels (0.12 +/- 0.03 U/ml, P < 0.001) and bioactivity (0.12 +/- 0.04 U/ml, P < 0.001) were significantly lower in the hypothyroid group. Liver IGF-I mRNA levels were not statistically different in the control and hyperthyroid animals, but were significantly reduced in the hypothyroid animals (P < 0.05 vs control). Heart IGF-I mRNA levels were similar in the control and hypothyroid rats, but were significantly increased in the hyperthyroid and treated hypothyroid animals (increased by 32% in hyperthyroidism, P < 0.05; increased by 57% in treated hypothyroidism, P < 0.01). Cardiac IGF-I was significantly elevated in hyperthyroidism (0.16 +/- 0.01 U/mg heart tissue, P < 0.01), was low in hypothyroidism (0.08 +/- 0.01 U/mg, P < 0.01) and was normalized in the treated hypothyroid group (0.11 +/- 0.01 U/mg vs control, 0.13 +/- 0.01 U/mg). Low body mass during both hypothyroidism and hyperthyroidism is therefore associated with reduced systemic IGF bioactivity. In hypothyroidism there is a primary defect in the endocrine function of IGF-I, while in hyperthyroidism serum IGF bioactivity is reduced in the presence of normal endocrine production of this anabolic hormone.(ABSTRACT TRUNCATED AT 400 WORDS)
甲状腺激素对许多组织的正常生长和发育至关重要。在大鼠中，甲状腺功能减退与生长发育受损有关，甲状腺功能亢进则与高分解代谢状态及骨骼肌消瘦相关，但矛盾的是，还会导致心脏肥大。甲状腺激素产生心脏肥大和肌球蛋白同工酶变化的机制尚不清楚。在本研究中，对甲状腺功能亢进、减退及对照大鼠，研究了具有旁分泌和内分泌作用的合成代谢激素胰岛素样生长因子-I（IGF-I）在产生心脏肥大中的作用。还纳入了一个经过治疗的甲状腺功能减退组，以评估甲状腺功能急性恢复正常的效果。与对照组（618.5±28.6克）相比，甲状腺功能亢进组（平均±标准误；535.5±24.9克，P<0.05）、甲状腺功能减退组（245.3±9.8克，P<0.001）和经过治疗的甲状腺功能减退组（265.3±9.8克，P<0.001）动物的体重显著降低。然而，与对照组（2.26±0.03×10⁻³）相比，甲状腺功能亢进组（2.74±0.11×10⁻³，P<0.01）和经过治疗的甲状腺功能减退组（2.87±0.07×10⁻³，P<0.001）动物的心脏重量/体重比显著增加。对照组和甲状腺功能亢进组大鼠的血清IGF-I浓度相似（0.91±0.07对0.78±0.04 U/ml，P=0.26），但甲状腺功能亢进血清中的生物活性降低了70%，提示存在IGF的循环抑制剂。甲状腺功能减退组的血清IGF-I水平（0.12±0.03 U/ml，P<0.001）和生物活性（0.12±0.04 U/ml，P<0.001）显著降低。对照组和甲状腺功能亢进动物的肝脏IGF-I mRNA水平无统计学差异，但甲状腺功能减退动物的该水平显著降低（与对照组相比，P<0.05）。对照组和甲状腺功能减退大鼠的心脏IGF-I mRNA水平相似，但甲状腺功能亢进和经过治疗的甲状腺功能减退动物的该水平显著升高（甲状腺功能亢进时升高32%，P<0.05；经过治疗的甲状腺功能减退时升高57%，P<0.01）。甲状腺功能亢进时心脏IGF-I显著升高（0.16±0.01 U/mg心脏组织，P<0.01），甲状腺功能减退时较低（0.08±0.01 U/mg，P<0.01），经过治疗的甲状腺功能减退组恢复正常（与对照组相比为0.11±0.01 U/mg，对照组为0.13±0.01 U/mg）。因此，甲状腺功能减退和亢进时的低体重均与全身IGF生物活性降低有关。甲状腺功能减退时IGF-I的内分泌功能存在原发性缺陷，而甲状腺功能亢进时，在这种合成代谢激素内分泌产生正常的情况下，血清IGF生物活性降低。（摘要截短至400字）
