转运蛋白与激素结合的临床意义
绝大多数激素转运蛋白对血清中激素水平的调控主要依靠转运蛋白数量的改变而非其与激素亲和力的改变。正常情况下转运蛋白的波动并不会引起激素水平和代谢的变化，转运蛋白对激素的影响是多方面的。甲状腺激素转运蛋白主要的作用是维持甲状腺外激素池的相对稳定，并保证每分钟向组织释放＜0.5%的FT4用于正常的生命活动。可以预见，在无甲状腺激素供给的情况下，如果甲状腺转运蛋白缺失，循环中的甲状腺激素会在几个小时内耗竭；但如果甲状腺转运蛋白尤其是TBG正常的情况下，在未来的24h内T3和T4只会出现10%和40%的下降。由此我们得出结论，血清甲状腺转运蛋白可以在激素浓度突然发生波动时保持机体在短时间内对激素的利用不发生紊乱。
转运蛋白同甲状腺激素结合第二可能的功能是对碘消耗的额外保护，由于其同富含碘的甲状腺激素相结合，赋予了小分子碘元素大分子的性质，从而限制其从尿液中流出。在一些对鱼类的研究中发现，鱼类缺乏高亲和性的T4结合蛋白，这一现象可能归因于鱼栖息的环境中富含碘，不需要对碘排泄的特殊保护，这也从反方向验证了转运蛋白防止碘流失的作用。
在动物肝脏灌流的研究中提示了转运蛋白的第三个功能，实验发现转运蛋白灌注过的肝脏组织有助于甲状腺激素均匀分布，这一作用可以使血液循环中甲状腺激素水平的变化迅速传达给所有相关靶细胞[29]。
转运蛋白的第四个功能实施模式类似与皮质醇结合球蛋白，它可以根据激素输送位点的特异性及酶的变化，通过调整TBG水平控制激素的输送量。例如，中性粒细胞弹性蛋白酶可以将TBG的结构变换为耐热性的TBG，这种形式的TBG同T4的结合力减弱。
另外，通过相关动物的研究也发现了甲状腺激素转运蛋白其他的作用，详见表8-4。如人们发现TBG与野猪睾丸的大小存在一定相关性。其分子机制可能是由于当野猪在226位的密码子是组氨酸而不是天冬酰胺的情况下，TBG同T4的亲和力较低，同时野猪的睾丸也较小，青春期发病较早。
总之，甲状腺激素的转运蛋白，它们共同作用，维持着甲状腺激素水平的平衡，它们单独变化可能不会导致机体的疾病状态。另一方面，TBG、TTR和其他一些次要的转运蛋白（如Lp）还存在额外的生理和病理功能。
表8-4 甲状腺转运蛋白的可能功能及相关依据
续表
注：α1 -ACT为α1-抗胰凝乳蛋白酶。α1-AGP为 α1 -酸性糖蛋白。α1- AT 1为α1 -抗胰蛋白酶。AFP为甲胎蛋白。Apos为载脂蛋白。CBG为皮质激素结合球蛋白。HDL为高密度脂蛋白。HDL-R为高密度脂蛋白受体。LDL为低密度脂蛋白。LDL-R为低密度脂蛋白受体。Serpins为丝氨酸蛋白酶抑制剂。SHBG为性激素结合球蛋白。LCAT为卵磷脂-胆固醇乙酰转移酶。LPL为 脂蛋白脂肪酶。
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