Harris A R, Fang S L, Vagenakis A G, Braverman L E
Metabolism. 1978 Nov;27(11):1680-90. doi: 10.1016/0026-0495(78)90290-1.
To evaluate the effect of starvation, oral and i.v. nutriments, and hypothyroidism on the peripheral conversion of thyroxine (T4) to 3,3', 5-triiodothyronine (T3) in the rat and mouse, an in vitro system for assessing T4 conversion to T3 by fresh liver homogenates was used. A 2-day starvation in the rat reduced hepatic T3 generation from T4 by 47% +/- 3.5% (mean +/- SE) in six separate experiments and also impaired the metabolism of 125I-r-T3. Administration of carbohydrate (CHO) and amino acids (P), but not lipid (L), significantly increased T3 generation above values observed in the starved rat. The mean serum glucose concentration was similar in all nutriment-infused groups, but serum insulin was significantly greater in the CHO- and P-infused as compared to the L-infused rats. These findings suggest that CHO and P, but not L, are important modulators of hepatic outer ring thyronine deiodination in the rat, perhaps due to increased intracellular glucose. Hypothyroidism in the rat induced by thyroidectomy and congenital secondary hypothyroidism in the dwarf mouse resulted in a striking decrease in hepatic conversion of T4 to T3. This decrease was restored to normal by the daily s.c. administration of physiologic doses of T4 (1.5 microgram/100 g) or T3 (0.5 microgram/100 g) for 14 days, and was increased above normal following treatment of normal rate with greater than physiologic doses of T4 (3microgram/100 g) or T3 (1 microgram/100g). In vitro hepatic conversion of T4 to T3 is, therefore, dependent upon thyroid function. Since 2-days starvation in the rat was associated with decreased serum concentrations of T4, T3, and TSH, and hypothyroidism resulted in decreased conversion of T4 to T3, the effect of a constant 2-day infusion of physiologic doses of T4 or T3 in the starved rat on the in vitro deiodination of T4 was assessed. Thyroid hormone replacement did not enhance the conversion of T4 to T3 in the starved rat. These observations suggest that the starvation-induced decrease in hepatic generation of T3 from T4 is not due to hypothyroidism and that the mechanism(s) of the decreased T3 production observed in starvation and hypothyroidism is different.
为评估饥饿、口服及静脉营养以及甲状腺功能减退对大鼠和小鼠外周甲状腺素（T4）向3,3',5-三碘甲状腺原氨酸（T3）转化的影响，采用新鲜肝匀浆体外评估T4向T3转化的系统。在六项独立实验中，大鼠2天饥饿使肝脏由T4生成T3的量减少47%±3.5%（均值±标准误），并损害了125I - r - T3的代谢。给予碳水化合物（CHO）和氨基酸（P），而非脂质（L），可使T3生成量显著高于饥饿大鼠。所有营养输注组的平均血清葡萄糖浓度相似，但与输注L的大鼠相比，输注CHO和P的大鼠血清胰岛素显著更高。这些发现表明，CHO和P而非L是大鼠肝脏外环甲状腺原氨酸脱碘的重要调节因子，可能是由于细胞内葡萄糖增加所致。甲状腺切除诱导的大鼠甲状腺功能减退以及侏儒小鼠先天性继发性甲状腺功能减退导致肝脏T4向T3的转化显著降低。通过每天皮下注射生理剂量的T4（1.5微克/100克）或T3（0.5微克/100克）持续14天，这种降低可恢复正常，而用大于生理剂量的T4（3微克/克）或T3（1微克/100克）治疗正常大鼠后，转化增加至高于正常水平。因此，体外肝脏T4向T3的转化取决于甲状腺功能。由于大鼠2天饥饿与血清T4、T3和促甲状腺激素（TSH）浓度降低相关，且甲状腺功能减退导致T4向T3的转化减少，故评估了在饥饿大鼠中持续2天输注生理剂量的T4或T3对T4体外脱碘的影响。甲状腺激素替代并未增强饥饿大鼠中T4向T3的转化。这些观察结果表明，饥饿诱导的肝脏由T4生成T3减少并非由于甲状腺功能减退，且饥饿和甲状腺功能减退中观察到的T3生成减少的机制不同。
