W-Compound can be used as a Biomarker for Fetal Thyroid Function and a Potential Tool for Screening Congenital Hypothyroidism.
W-Compound can be used as a Biomarker for Fetal Thyroid Function and a Potential Tool for Screening Congenital Hypothyroidism.
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发表时间：
2022
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通讯作者：
Fucito ME
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作者：
Wu SY;Zhao H;Xi BX;Chen DB;Fucito ME
硫代偶联是甲状腺激素(TH)代谢的主要途径，在妊娠期间通过磺基转移酶(Sult)和3型脱碘酶将T4转化为非活性代谢物T4s、rT3s和T3s。与T4S和rT3S的高生成率一致，在绵羊和人类胎儿和早产儿中，存在高水平的血清硫化碘甲状腺原氨酸类似物，包括T4S、T3S、rT3S和3，3‘-T2S(T2S)。胎儿TH代谢途径预测T2S是胎儿中主要的TH代谢物。由于母体T2S的数量似乎来自胎儿的T3(活跃的TH)，母体隔室中的T2S量与绵羊胎儿的甲状腺功能相关。在人类中，母体血清含有高水平的可放射免疫分析的T2S；然而，它在HLPC上显示为与合成的T2S相邻但不相同的峰，我们将其命名为W-化合物。W-化合物的水平在怀孕期间增加，最高可达非怀孕妇女的20倍。正常和甲亢组孕妇血清W-化合物水平与胎儿T4和W-化合物浓度显著相关，而与孕妇血清T4水平无相关性，表明胎儿和母亲在TH代谢方面存在明显差异。胎儿T2S通过胎盘主动转移到母亲体内，母体体内的T2S或其代谢产物(W化合物)的数量反映了胎儿的甲状腺功能。因此，母体血清W-化合物可能是监测胎儿宫内甲状腺功能的生物标志物，但是否可以作为筛查/治疗甲状腺激素代谢异常所致先天性甲状腺功能减退的替代策略，还需要更多的研究。
Sulfoconjugation is the major pathway for thyroid hormone (TH) metabolism, converting T4 to inactive metabolites, T4S, rT3S, and T3S in fetus, via sulfotransferases (SULT) and type 3 deiodinase in gestation. Consistent with high production rate of T4S and rT3S, there are high serum sulfated iodothyronine analogs, including T4S, T3S, rT3S, and 3,3’-T2S (T2S), in ovine and human fetal and preterm infants. Fetal TH metabolic pathways predict T2S as the major TH metabolite in the fetus. Since maternal T2S appears to be quantitatively derived from fetal T3 (the active TH), the amount of T2S in the maternal compartment correlates with fetal thyroid function in sheep. In humans, maternal serum contains high levels of radioimmunoassayable T2S; however, it displays as a peak adjacent to but unidentical to synthetic T2S on HLPC and we named it the W-Compound. Levels of W-Compound increase during pregnancy and peak as high as 20-fold to that of nonpregnant women. Maternal serum levels of W-Compound significantly correlate with fetal T4 and W-compound concentrations but not maternal serum T4 in euthyroid or hyperthyroid women, showing a distinct difference between fetal and maternal in TH metabolism. Fetal T2S is actively transferred to the mother via placenta and the quantity of T2S or its metabolite (W-Compound) in maternal compartment reflects fetal thyroid function. Thus, maternal serum W-Compound may be a biomarker for monitoring fetal thyroid function in utero, although more investigations are needed to determine if it can be used as an alternative strategy for screening/managing congenital hypothyroidism due to dysregulated thyroid hormone metabolism.