INHIBITION OF THYROXINE TRANSPORT INTO CULTURED RAT HEPATOCYTES BY SERUM OF NONUREMIC CRITICALLY ILL PATIENTS - EFFECTS OF BILIRUBIN AND NONESTERIFIED FATTY-ACIDS
INHIBITION OF THYROXINE TRANSPORT INTO CULTURED RAT HEPATOCYTES BY SERUM OF NONUREMIC CRITICALLY ILL PATIENTS - EFFECTS OF BILIRUBIN AND NONESTERIFIED FATTY-ACIDS
复制标题
DOI：
10.1210/jc.76.5.1165
复制
发表时间：
1993-05-01
影响因子：
5.8
通讯作者：
HENNEMAN, G
中科院分区：
文献类型：
--
作者：
LIM, CF;DOCTER, R;HENNEMAN, G
我们研究了胆红素和油酸作为非尿毒症重症患者血浆T3降低的原因，这些患者血清甲状腺激素水平（T4≤60；T3≤1.1；rT3≥0.45 nmol/L）有显著变化且胆红素浓度升高（≥33 μmol/L）。当原代培养的大鼠肝细胞与这些患者的10%血清一起孵育时，[I - 125]T4产生的碘化物被抑制了42%。患者的血清白蛋白平均浓度降低了41%，而胆红素和非酯化脂肪酸（NEFA）浓度分别升高了2022%和115%。患者胆红素/白蛋白和NEFA/白蛋白的摩尔比分别为0.42和3.18。向10%正常人血清（白蛋白，70 μmol/L；NEFA，54 μmol/L；胆红素，1.1 μmol/L）中添加油酸（50 - 400 μmol/L）和胆红素（3 - 130 μmol/L）会逐渐抑制大鼠肝细胞产生碘化物。碘化物产生减少被推测是由于T4转运进入肝细胞受到抑制。大鼠肝微粒体对rT3的脱碘作用在游离胆红素和游离油酸浓度高达0.1 μmol/L时未发生改变。这些游离浓度比非甲状腺疾病中达到的浓度至少高1个数量级。重症患者（n = 12）血清对碘化物产生的抑制与胆红素/白蛋白（r = 0.72；P < 0.01）和NEFA/白蛋白（r = 0.58；P < 0.05）的摩尔比显著相关。对血清进行大量透析或用活性炭处理并不能完全去除对碘化物产生的抑制活性。重症患者血清中硫酸吲哚酚、3 - 羧基 - 4 - 甲基 - 5 - 丙基 - 2 - 呋喃丙酸和马尿酸（其他已知的肝细胞T4转运抑制剂）的浓度与正常受试者相似。这项研究以及碳水化合物对T3新生的众所周知的影响表明，在非尿毒症重症疾病中，胆红素和NEFA升高以及白蛋白水平降低可能至少部分是导致T3产生组织（如肝脏）中T4转运抑制以及这些重症患者血浆T3水平低的原因。对于甲状腺激素水平仅有轻微变化且胆红素和NEFA浓度较低的其他非甲状腺疾病患者，是否也存在肝细胞T4转运抑制剂这一问题仍有待确定。
We investigated bilirubin and oleic acid as causes of low plasma T3 in nonuremic critically ill patients with gross changes in serum thyroid hormone levels (T4, less-than-or-equal-to 60; T3, less-than-or-equal-to 1.1; rT3, greater-than-or-equal-to 0.45 nmol/L) and elevated bilirubin concentrations (greater-than-or-equal-to 33 mumol/L). Iodide production from [I-125]T4 was inhibited by 42% when rat hepatocytes in primary cultures were incubated with 10% serum from these patients. The mean serum concentration of albumin was reduced by 41%, while the concentrations of bilirubin and nonesterified fatty acids (NEFA) were increased by 2022% and 115%, respectively, in the patients. The molar ratios of bilirubin/albumin and NEFA/albumin in the patients were 0.42 and 3.18, respectively.Addition of oleic acid (50-400 mumol/L) and bilirubin (3-130 mumol/L) to 10% normal human serum (albumin, 70 Amol/L; NEFA, 54 mumol/L; bilirubin, 1.1 mumol/L) progressively inhibited the production of iodide by rat hepatocytes. The decreased iodide production was presumed to be caused by inhibition of T4 transport into hepatocytes. The deiodination of rT3 by rat liver microsomes was unaltered by free bilirubin and free oleic acid concentrations up to 0.1 mumol/L. These free concentrations are at least 1 order of magnitude higher than that attained in nonthyroidal illness.The inhibition of iodide production by the sera of critically ill patients (n = 12) was significantly correlated with the molar ratios of bilirubin/albumin (r = 0.72; P < 0.01) and NEFA/albumin (r = 0.58; P < 0.05). Extensive dialysis or treatment of the sera with charcoal did not completely remove the inhibitory activity on iodide production. Serum concentrations of indoxyl sulfate, 3-carboxy-4-methyl-5-propyl-2-furan propanoic acid, and hippuric acid in the critically ill patients (other known T4 transport inhibitors into hepatocytes) were similar to those in the normal subjects.This study together with the well known effects of carbohydrate on T3 neogenesis suggest that elevated bilirubin and NEFA and the low albumin level in non-uremic critical illness may be at least partly responsible for the T4 transport inhibition in T3-producing tissues (e.g. the liver) and, thus, the low plasma T3 levels in these critically ill patients. The question of whether inhibitors of T4 transport into the hepatocytes are also present in other patients with nonthyroidal illness who show only mild changes in thyroid hormone levels and have low concentrations of bilirubin and NEFA remains to be determined.