Vranckx R, Savu L, Maya M, Nunez E A
U.224, INSERM, CNRS, Faculté de Médecine Xavier Bichat, Laboratoire de Biochimie, Paris, France.
Biochem J. 1990 Oct 15;271(2):373-9. doi: 10.1042/bj2710373.
We confirm our finding of a major development-regulated thyroxine-binding globulin (TBG) in the serum of the euthyroid mouse and investigate a number of its binding, structural and regulatory properties. Between 16 days foetal and 60 days postnatal life, the thyroxine (T4)- and tri-iodothyronine (T3)-binding activities of the sera show a striking ontogenic pattern: the binding is 2-3 times higher in foetuses than in mothers, then further increases after birth, reaching between 3 and 5 days maximum values which are 7-8 times higher than the adult ones. This pattern is not correlated with the ontogenesis of the acknowledged specific (transthyretin, TTR) and non-specific (albumin, alpha 1-foetoprotein) thyroid-hormone carriers of the mouse sera. PAGE studies demonstrate that the protein responsible for the elevated binding of the perinatal period is an alpha 1-globulin, with a migration similar to that of human and rat TBGs. Scatchard analysis is consistent with the notions that the T4-binding sites of TBG have high association constants, about two orders of magnitude above the T4 sites of TTR (10(9) M-1 as against 10(7) M-1) and low capacities (37 and 4 nmol/g of serum proteins in pups and adults respectively). Isoelectric focusing (i.e.f.) demonstrates that mouse TBG is a microheterogeneous protein separable, as a function of the pH gradient, in up to 10-12 isoforms, Marked shifts of the relative abundance of isoforms in the course of development are evidenced. The modulation of the TBG binding activity by non-esterified fatty acids (NEFA) and the control of its synthesis by the thyroid status are also reported. Mono- and poly-unsaturated NEFAs are strong inhibitors of the TBG, although they affect TTR less readily. On the other hand, the biosynthesis and/or secretion of TBG, but not of TTR, is under thyroid-hormone control, experimental hypothyroidism inducing a marked increase of the serum TBG. The TBG of mouse behaves as a highly significant parameter of development, pointing to a likely important function of the protein in the process of maturation. Our finding of major TBGs in both euthyroid rats and mice suggests that TBG is more widely spread than was thought until now, but difficult to detect in certain species outside definite maturation stages.
我们证实了在甲状腺功能正常的小鼠血清中发现了一种主要受发育调节的甲状腺素结合球蛋白（TBG），并研究了其一些结合、结构和调节特性。在胎儿期16天到出生后60天之间，血清中甲状腺素（T4）和三碘甲状腺原氨酸（T3）的结合活性呈现出显著的个体发育模式：胎儿期的结合活性比母体高2 - 3倍，出生后进一步升高，在出生后3至5天达到最大值，比成年小鼠高7 - 8倍。这种模式与小鼠血清中公认的特异性（甲状腺素转运蛋白，TTR）和非特异性（白蛋白、α1 - 胎儿蛋白）甲状腺激素载体的个体发育无关。聚丙烯酰胺凝胶电泳（PAGE）研究表明，负责围产期结合活性升高的蛋白质是一种α1球蛋白，其迁移率与人及大鼠的TBG相似。Scatchard分析结果与以下观点一致：TBG的T4结合位点具有高结合常数，比TTR的T4位点高约两个数量级（分别为10⁹ M⁻¹和10⁷ M⁻¹），且结合容量较低（幼崽和成年小鼠血清蛋白中分别为37和4 nmol/g）。等电聚焦（IEF）表明，小鼠TBG是一种微不均一蛋白质，根据pH梯度可分离出多达10 - 12种同工型，在发育过程中同工型的相对丰度有明显变化。还报道了非酯化脂肪酸（NEFA）对TBG结合活性的调节以及甲状腺状态对其合成的控制。单不饱和和多不饱和NEFA是TBG的强抑制剂，尽管它们对TTR的影响较小。另一方面，TBG的生物合成和/或分泌受甲状腺激素控制，而TTR不受其控制，实验性甲状腺功能减退会导致血清TBG显著增加。小鼠的TBG表现为发育的一个高度重要参数，表明该蛋白质在成熟过程中可能具有重要功能。我们在甲状腺功能正常的大鼠和小鼠中均发现主要的TBG，这表明TBG的分布比目前认为的更为广泛，但在某些物种的特定成熟阶段之外难以检测到。
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