Qualitative and quantitative differences in the pathways of extrathyroidal triiodothyronine generation between euthyroid and hypothyroid rats.
Qualitative and quantitative differences in the pathways of extrathyroidal triiodothyronine generation between euthyroid and hypothyroid rats.
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甲状腺功能正常和甲状腺功能减退大鼠甲状腺外三碘甲状腺原氨酸生成途径的定性和定量差异。
DOI：
10.1172/jci111313
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发表时间：
1984
期刊：
影响因子：
--
通讯作者：
Larsen,PR
中科院分区：
文献类型：
--
作者：
Silva,JE;Gordon,MB;Crantz,FR;Leonard,JL;Larsen,PR
丙基硫尿嘧啶（PTU）对肝脏和肾脏碘甲状腺原氨酸5′-脱碘酶活性（5′d - i）的最大抑制剂量，仅能使甲状腺功能正常的大鼠甲状腺外T4到T3的转化减少60-70%。在垂体、中枢神经系统和棕色脂肪组织中发现了T4到T3转化的第二个途径（5'D-II）。5'D-II对PTU不敏感，在甲状腺功能减退症中增加，而在甲状腺功能减退大鼠中5'D-I减少。采用非室区分析方法，对注射[125I]T4和[131I]T3后甲状腺正常和去甲状腺大鼠甲状腺素（T4）和三碘甲状腺原氨酸（T3）的动力学进行了评价。甲状腺状态对血浆T4的分布体积和分级清除率均无影响，但甲状腺功能减退大鼠的分级清除率约降低50% （P < 0.001）。甲状腺功能正常的大鼠T4到T3的转化率为22%，甲状腺功能低下的大鼠为26%。在甲状腺功能正常的大鼠中，足够的PTU抑制肝脏和肾脏的5'D-I大于90%，使[125I]T4后血清[125I]T3降低（结果以每毫升剂量百分比× 10(-3) +/- SEM表示）：4小时，对照组16 +/- 2 vs. PTU 4 +/- 1, P < 0.005； 22小时，对照组6.4 +/- 0.4 vs. PTU 3.6 +/- 0.7, P < 0.025。在去甲状腺大鼠中，相同剂量的PTU也能抑制肝脏和肾脏中的5'D-I，但对血清[125I]T4生成[125I]T3没有影响。同样，给甲状腺切除大鼠1微克T4/100 g bw后，对照组血清T3（放射免疫测定）增加0.30 +/- 0.6 ng/ml， ptu治疗大鼠血清T3（放射免疫测定）增加0.31 +/- 0.09 ng/ml。然而，当T4剂量增加到2 ~ 10微克/100 g bw时，PTU预处理显著降低了血清T3的增加。甲状腺功能减退大鼠T3清除率不受PTU影响。在脑、垂体和棕色脂肪组织中，通过30微克/100克bw的反向T3 (rT3), 5'D-II减少到小于或等于对照组的60%，这种效果在rT3清除后至少持续3小时。在rt3预处理的去甲状腺大鼠中，血清中[125I]T4示踪剂[125I]T3的生成减少：6 +/- 1比12 +/- 1 × 10(-3)%剂量/ml， P < 0.01。我们得出结论，低剂量外源性T4给甲状腺功能减退大鼠产生的几乎所有T3都是通过ptu不敏感途径产生的，可能是由5'D-II催化的。这是低Km酶活性增强的结果，同时伴有甲状腺功能减退状态下肝脏和肾脏5' d - 1特征的降低。结果表明，在某些情况下，5D-II活性可能有助于细胞外和细胞内的T3池。
Propylthiouracil (PTU) in maximally inhibitory doses for liver and kidney iodothyronine 5'-deiodinase activity (5'D-I), reduces extrathyroidal T4 to T3 conversion by only 60-70% in euthyroid rats. A second pathway of T4 to T3 conversion (5'D-II) has been found in pituitary, central nervous system, and brown adipose tissue. 5'D-II is insensitive to PTU and increases in hypothyroidism, whereas 5'D-I decreases in hypothyroid rats. Thyroxine (T4) and triiodothyronine (T3) kinetics were assessed in euthyroid and thyroidectomized rats by noncompartmental analysis after injecting [125I]T4 and [131I]T3. Neither the volume of distribution nor the rate of fractional removal of plasma T4 was affected by the thyroid status, but the fractional removal rate of T3 was approximately 50% reduced in hypothyroid rats (P less than 0.001). Fractional T4 to T3 conversion was 22% in euthyroid and 26% in hypothyroid rats. In euthyroid rats, sufficient PTU to inhibit liver and kidney 5'D-I greater than 90% reduced serum [125I]T3 after [125I]T4 (results given as percent dose per milliliter X 10(-3) +/- SEM): 4 h, control 16 +/- 2 vs. PTU 4 +/- 1, P less than 0.005, and 22 h, control 6.4 +/- 0.4 vs. PTU 3.6 +/- 0.7, P less than 0.025. In thyroidectomized rats, the same dose of PTU also inhibited 5'D-I in liver and kidney, but had no effect on the generation of serum [125I]T3 from [125I]T4. Similarly, after 1 microgram T4/100 g bw was given to thyroidectomized rats, serum T3 (radioimmunoassay) increased by 0.30 +/- 0.6 ng/ml in controls and 0.31 +/- 0.09 ng/ml in PTU-treated rats. However, when the dose of T4 was increased to 2-10 micrograms/100 g bw, PTU pretreatment significantly reduced the increment in serum T3. T3 clearance was not affected by PTU in hypothyroid rats. The 5'D-II in brain, pituitary, and brown adipose tissue was reduced to less than or equal to 60% of control by 30 micrograms/100 g bw reverse T3 (rT3), an effect that lasted for at least 3 h after rT3 had been cleared. In rT3-pretreated thyroidectomized rats, the generation of [125I]T3 from tracer [125I]T4 was reduced in the serum: 6 +/- 1 vs. 12 +/- 1 X 10(-3)% dose/ml, P less than 0.01, during this 3-h period. We conclude that virtually all the T3 produced from low doses of exogenous T4 given to hypothyroid rats is generated via a PTU-insensitive pathway, presumably catalyzed by the 5'D-II. This is a consequence of the enhanced activity of this low Km enzyme together with the concomitant decrease in the hepatic and renal 5'D-I characteristic of the hypothyroid state. The results indicate that in some circumstances, 5D-II activity may contribute to the extracellular, as well as intracellular, T3 pool.
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大鼠肾匀浆中 L-甲状腺素转化为三碘甲状腺原氨酸。
影响因子：
4.8
作者：
P. Chiraseveenuprapund;U. Buergi;A. Goswami;I. Rosenberg
通讯作者：
I. Rosenberg
用于放射免疫测定的最大比活性的 125I 单标记 3,5,3-三碘甲状腺原氨酸和甲状腺素的合成。
影响因子：
2.1
作者：
J. Weeke;H. Orskov
通讯作者：
H. Orskov
影响因子：
4.8
作者：
DISTEFANO, JJ;JANG, M;BROUTMAN, M
通讯作者：
BROUTMAN, M
大鼠体内 L-甲状腺素甲状腺外转化为 3,5,3-三碘-L-甲状腺氨酸的定量。
影响因子：
15.9
作者：
H. L. Schwartz;M. Surks;J. Oppenheimer
通讯作者：
J. Oppenheimer
估计人体中甲状腺素和三碘甲状腺原氨酸的分布以及甲状腺素到三碘甲状腺原氨酸的转化率。
影响因子：
15.9
作者：
M. Inada;K. Kasagi;S. Kurata;Y. Kazama;H. Takayama;K. Torizuka;M. Fukase;T. Soma
通讯作者：
T. Soma