Effect of experimentally induced hypothyroidism on sulfate renal transport in rats.
Decreased serum sulfate concentrations are observed in hypothyroid patients. However, the mechanism involved in thyroid hormone-induced alterations of renal sulfate homeostasis is unknown. The objectives of this investigation were to determine the effect of 6-propyl-2-thiouracil (PTU)-induced hypothyroidism in rats on 1) the in vivo serum concentrations, renal clearance, and renal reabsorption of sulfate, 2) the in vitro renal transport in brush-border membrane (BBM) and basolateral membrane (BLM) vesicles, and 3) the cellular mechanism of the hypothyroid-induced alteration in sulfate renal transport. Serum sulfate concentrations, renal fractional reabsorption of sulfate, and creatinine clearance were decreased significantly in the hypothyroid group. The Vmax values for sodium-sulfate cotransport in BBM were significantly decreased in the kidney cortex from the hypothyroid animals (0.90 +/- 0.31 vs. 0.49 +/- 0.08 nmol. mg-1. 10 s-1, n = 5-6, P < 0.05) without changes in Km. There were no significant differences in Vmax and Km for sulfate/anion exchange transport in BLM. Sodium-dependent sulfate transporter (NaSi-1) mRNA and protein levels were significantly lower in the kidney cortex from hypothyroid rats. Hypothyroidism did not alter the membrane motional order (fluidity) in BBM and BLM, which indicates that the changes in the membrane fluidity do not represent the mechanism for the altered renal transport. These results demonstrate that PTU-induced hypothyroidism decreases sodium-sulfate cotransport by downregulation of the NaSi-1 gene.
Sagawa
K
K
Department of Pharmaceutics, State University of New York at Buffalo, Amherst, New York 14260, USA.
Murer
H
H
Morris
M E
ME
D000818:Animals; D001692:Biological Transport / Q000502:physiology; D002352:Carrier Proteins / Q000235:genetics / Q000378:metabolism; D027682:Cation Transport Proteins; D005260:Female; D007037:Hypothyroidism / Q000378:metabolism*; D007668:Kidney / Q000378:metabolism*; D008560:Membrane Fluidity / Q000502:physiology; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D011917:Rats, Inbred Lew; D000077003:Sodium Sulfate Cotransporter; D013431:Sulfates / Q000378:metabolism*; D027981:Symporters
D002352:Carrier Proteins; D027682:Cation Transport Proteins; D012333:RNA, Messenger; D000077003:Sodium Sulfate Cotransporter; D013431:Sulfates; D027981:Symporters