Mohebbi Nilufar, Kovacikova Jana, Nowik Marta, Wagner Carsten A
Institute of Physiology, University of Zurich, Winterthurerstrasse 190, CH-8057 Zurich, Switzerland.
Am J Physiol Renal Physiol. 2007 Jul;293(1):F416-27. doi: 10.1152/ajprenal.00391.2006. Epub 2007 Apr 4.
Hypothyroidism in humans is associated with incomplete distal renal tubular acidosis, presenting as the inability to respond appropriately to an acid challenge by excreting less acid. Here, we induced hypothyroidism in rats with methimazole (HYPO) and in one group substituted with l-thyroxine (EU). After 4 wk, acid-base status was similar in both groups. However, after 24 h acid loading with NH(4)Cl HYPO rats displayed a more pronounced metabolic acidosis. The expression of the Na(+)/H(+) exchanger NHE3, the Na(+)-phosphate cotransporter NaPi-IIa, and the B2 subunit of the vacuolar H(+)-ATPase was reduced in the brush-border membrane of the proximal tubule of the HYPO group, paralleled by a lower abundance of the Na(+)/HCO(3)(-) cotransporter NBCe1 and a higher expression of the acid-secretory type A intercalated cell-specific Cl(-)/HCO(3)(-) exchanger AE1. In contrast to control conditions, the expression of NBCe1 was increased in the HYPO group during metabolic acidosis. In addition, net acid excretion was similar in both groups. The relative number of type A intercalated cells was increased in the connecting tubule and cortical collecting duct of the HYPO group during acidosis. Thus thyroid hormones modulate the renal response to an acid challenge and alter the expression of several key acid-base transporters. Mild hypothyroidism is associated only with a very mild defect in renal acid handling, which appears to be mainly located in the proximal tubule and is compensated by the distal nephron.
人类甲状腺功能减退与不完全性远端肾小管酸中毒有关，表现为无法通过减少酸排泄来对酸负荷做出适当反应。在此，我们用甲巯咪唑诱导大鼠甲状腺功能减退（HYPO组），并对其中一组用左旋甲状腺素替代（EU组）。4周后，两组的酸碱状态相似。然而，在给予氯化铵进行24小时酸负荷后，HYPO组大鼠表现出更明显的代谢性酸中毒。HYPO组近端小管刷状缘膜中钠/氢交换体NHE3、钠-磷酸盐共转运体NaPi-IIa和液泡型氢-ATP酶的B2亚基表达降低，同时钠/碳酸氢根共转运体NBCe1丰度降低，酸分泌型A闰细胞特异性氯/碳酸氢根交换体AE1表达升高。与对照条件相比，代谢性酸中毒期间HYPO组中NBCe1的表达增加。此外，两组的净酸排泄相似。酸中毒期间，HYPO组连接小管和皮质集合管中A闰细胞的相对数量增加。因此，甲状腺激素调节肾脏对酸负荷的反应，并改变几种关键酸碱转运体的表达。轻度甲状腺功能减退仅与肾脏酸处理方面非常轻微的缺陷有关，该缺陷似乎主要位于近端小管，并由远端肾单位代偿。
