Liang H, Juge-Aubry C E, O'Connell M, Burger A G
Department of Medicine, Hôpital Cantonal Universitaire, Geneva, Switzerland.
Eur J Endocrinol. 1997 Nov;137(5):537-44. doi: 10.1530/eje.0.1370537.
In order to compare the effect of 3,5,3'-triiodothyroacetic acid (TRIAC) with those of triiodothyronine (T3) and thyroxine (T4), severely hypothyroid rats (n=56) were infused over 13 days with 1, 2 or 4 nmol/100 g body weight (BW) per day of T3 or 2, 4 or 8 nmol/100 g BW per day of T4 or TRIAC. The 8 nmol/100 g BW per day of T4 or TRIAC induced the same increase in resting metabolic rate, yet 4 nmol/100 g BW per day of T3 was more potent (P < 0.05). For inhibiting serum TSH levels, 2 nmol/100 g BW per day of TRIAC were significantly less active than 2 nmol/100 g BW per day of T4 or 1 nmol/100 g BW per day of T3 (TRIAC, serum TSH 35.5 +/- 5.7; T3 2.58 +/- 0.91; T4 2.12 +/- 0.59 ng/ml). At higher doses serum TSH and beta-TSH mRNA were unmeasurable. Using serum T3 levels as covariate, the action of T3 and T4 was identical on cardiac monodeiodinase type 1 (5'D1) activity and hepatic malic enzyme (Me) mRNA levels and similar for hepatic 5'D1 activity. The effect of TRIAC was compared with T3 by using increasing doses of 1, 2 and 4 nmol/100 g BW per day of T3 and 2, 4 and 8 nmol/100 g BW per day of TRIAC. ANOVA indicated that there was no major difference between the effects of the hormones since with increasing doses the response of hepatic 5'D1 mRNA levels and enzyme activity and Me mRNA remained parallel. However, when studying the effect on cardiac 5'D1 activity there was not only a difference for type of treatment (T3 > TRIAC) but this difference became greater with each increment in dose. Interestingly there was also only a small effect of TRIAC on increase in heart weight compared with T3 and T4. Brain cortex monodeiodinase type 2 (5'D2) was mainly inhibited by T4 infusions. Monodeiodinase type 3 (5'D3) was stimulated by T4, less so by TRIAC and least by T3, expressing probably the local T3 and TRIAC concentrations. In conclusion, despite apparently similar effects of TRIAC and T3 and T4 on hepatic parameters of thyroid hormone action, TRIAC differs considerably in terms of its effects on cardiac 5'D1 activity and possibly on other fundamental effects of thyroid hormones on the heart since heart weight increased significantly less with TRIAC than with T3 or T4.
为了比较3,5,3'-三碘甲状腺乙酸（TRIAC）与三碘甲状腺原氨酸（T3）和甲状腺素（T4）的作用效果，对56只严重甲状腺功能减退的大鼠进行了为期13天的灌注，每天分别给予1、2或4 nmol/100 g体重（BW）的T3，或2、4或8 nmol/100 g BW的T4或TRIAC。每天8 nmol/100 g BW的T4或TRIAC使静息代谢率升高的幅度相同，但每天4 nmol/100 g BW的T3作用更强（P < 0.05）。对于抑制血清促甲状腺激素（TSH）水平，每天2 nmol/100 g BW的TRIAC活性显著低于每天2 nmol/100 g BW的T4或每天1 nmol/100 g BW的T3（TRIAC组血清TSH为35.5±5.7；T3组为2.58±0.91；T4组为2.12±0.59 ng/ml）。在更高剂量下，血清TSH和β-TSH mRNA无法检测到。以血清T3水平作为协变量，T3和T4对心脏1型单碘甲状腺原氨酸脱碘酶（5'D1）活性和肝脏苹果酸酶（Me）mRNA水平的作用相同，对肝脏5'D1活性的作用相似。通过每天给予递增剂量的1、2和4 nmol/100 g BW的T3以及2、4和8 nmol/100 g BW的TRIAC，比较了TRIAC与T3的作用效果。方差分析表明，这些激素的作用之间没有重大差异，因为随着剂量增加，肝脏5'D1 mRNA水平、酶活性和Me mRNA的反应保持平行。然而，在研究对心脏5'D1活性的影响时，不仅治疗类型存在差异（T3 > TRIAC），而且这种差异随着剂量的每次增加而变得更大。有趣的是，与T3和T4相比，TRIAC对心脏重量增加的影响也较小。大脑皮质2型单碘甲状腺原氨酸脱碘酶（5'D2）主要受到T4灌注的抑制。3型单碘甲状腺原氨酸脱碘酶（5'D3）受到T4的刺激，受TRIAC的刺激较小，受T3的刺激最小，这可能反映了局部T3和TRIAC的浓度。总之，尽管TRIAC与T3和T4对甲状腺激素作用的肝脏参数的影响明显相似，但TRIAC在对心脏5'D1活性的影响以及可能对甲状腺激素对心脏的其他基本作用方面存在显著差异，因为TRIAC使心脏重量增加的幅度明显小于T3或T4。
