Thyroid hormone deficiency alters expression of acid-base transporters in rat kidney.
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.
Mohebbi
Nilufar
N
Institute of Physiology, University of Zurich, Winterthurerstrasse 190, CH-8057 Zurich, Switzerland.
Kovacikova
Jana
J
Nowik
Marta
M
Wagner
Carsten A
CA
D000138:Acidosis / Q000378:metabolism; D000643:Ammonium Chloride / Q000378:metabolism; D000818:Animals; D013956:Antithyroid Agents / Q000494:pharmacology; D001639:Bicarbonates / Q000378:metabolism; D015153:Blotting, Western; D002352:Carrier Proteins / Q000096:biosynthesis*; D004797:Enzyme-Linked Immunosorbent Assay; D006863:Hydrogen-Ion Concentration; D007037:Hypothyroidism / Q000378:metabolism; D007668:Kidney / Q000378:metabolism*; D007686:Kidney Tubules, Distal / Q000378:metabolism; D007687:Kidney Tubules, Proximal / Q000187:drug effects / Q000378:metabolism; D008297:Male; D008713:Methimazole / Q000494:pharmacology; D009399:Nephrons / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D000074083:Sodium-Hydrogen Exchanger 3; D017923:Sodium-Hydrogen Exchangers / Q000096:biosynthesis* / Q000235:genetics; D013963:Thyroid Hormones / Q000172:deficiency*; D013972:Thyrotropin / Q000097:blood; D014284:Triiodothyronine / Q000097:blood
D013956:Antithyroid Agents; D001639:Bicarbonates; D002352:Carrier Proteins; C000613385:SLC9A3 protein, human; C000613387:Slc9a3 protein, rat; D000074083:Sodium-Hydrogen Exchanger 3; D017923:Sodium-Hydrogen Exchangers; D013963:Thyroid Hormones; D000643:Ammonium Chloride; D014284:Triiodothyronine; D008713:Methimazole; D013972:Thyrotropin