Goumaz M O, Kaiser C A, Burger A G
Endocrinology. 1987 Apr;120(4):1590-6. doi: 10.1210/endo-120-4-1590.
T4 and reverse T3 (rT3) can inhibit 5'-deiodinase type II activity in rat brain cortex, pituitary, and brown adipose tissue, raising the possibility that T4 may act in vivo after conversion to rT3. The aim of this study was to measure in hypothyroid (Tx) rats the content of brain cortex rT3 during a constant 7-day infusion of either [125I]T4 alone, corresponding to 12 pmol T4/day X 100 g body weight (BW), or together with 400 pmol T4/day. [125I]T4, rT3, and T3 were extracted from brain cortex, pituitary, kidney, and liver with a combination of adsorption chromatography on Sephadex G-25, HPLC, and immunoprecipitation. [131I]T4, T3, or rT3 were used as internal standards. [125I]rT3 could be detected in brain cortex, liver, and kidney in Tx rats infused with [125I]T4 (12 pmol T4/day X 100 g BW) and in those infused with 400 pmol T4/day X 100 g BW. The highest rT3 concentrations were found in brain cortex, where it represented 6% to 10.5% of the local T4 concentration. During an infusion of 400 pmol T4/day X 100 g BW, brain cortex T3 concentration was 6 times higher in the brain cortex than in serum, and even exceeded that of T4. In Tx rats receiving [125I]T4 alone the brain cortex to serum T3 ratio was 3:1, but the total serum T3 concentration, measured by RIA, was much higher than that due to conversion [0.50 +/- (SE) 0.1 pmol/ml vs. 0.018 +/- 0.002 pmol T3/ml], indicating thyroidal secretion. The effect of the blood-brain barrier on rT3 was measured by infusing [125I]rT3 over 4 days. After killing, rT3 was isolated as above. Approximately 3% of serum rT3 was retrieved from the brain cortex, whereas during the T4 infusion 40-50% of serum rT3 was found demonstrating that brain cortex rT3 is locally produced.
T4和反式T3(rT3)可抑制大鼠大脑皮层、垂体和棕色脂肪组织中的II型5'-脱碘酶活性,这增加了T4在体内转化为rT3后可能发挥作用的可能性。本研究的目的是测量甲状腺功能减退(Tx)大鼠在持续7天输注单独的[125I]T4(相当于12 pmol T4/天×100 g体重(BW))或与400 pmol T4/天联合输注期间大脑皮层rT3的含量。通过在Sephadex G-25上进行吸附色谱、高效液相色谱(HPLC)和免疫沉淀相结合的方法,从大脑皮层、垂体、肾脏和肝脏中提取[125I]T4、rT3和T3。[131I]T4、T3或rT3用作内标。在输注[125I]T4(12 pmol T4/天×100 g BW)的Tx大鼠以及输注400 pmol T4/天×100 g BW的大鼠的大脑皮层、肝脏和肾脏中可检测到[125I]rT3。在大脑皮层中发现rT3浓度最高,其占局部T4浓度的6%至10.5%。在输注400 pmol T4/天×100 g BW期间,大脑皮层中的T3浓度比血清中的高6倍,甚至超过了T4的浓度。在仅接受[125I]T4的Tx大鼠中,大脑皮层与血清的T3比值为3:1,但通过放射免疫分析(RIA)测量的总血清T3浓度远高于转化产生的浓度[0.50±(标准误)0.1 pmol/ml对0.018±0.002 pmol T3/ml],表明存在甲状腺分泌。通过在4天内输注[125I]rT3来测量血脑屏障对rT3的影响。处死动物后,按上述方法分离rT3。从大脑皮层中回收了约3%的血清rT3,而在输注T4期间发现40 - 50%的血清rT3,这表明大脑皮层rT3是在局部产生的。