Role of thyroid hormone in regulation of renal phosphate transport in young and aged rats

Endocrinology. 1999 Apr;140(4):1544-51. doi: 10.1210/endo.140.4.6658.


In the present study, we have examined the cellular mechanisms mediating the regulation of renal proximal tubular sodium-coupled inorganic phosphate (Na/Pi) transport by thyroid hormone (T3) in young and aged rats. Young hypothyroid rats showed a marked decrease in Na/Pi cotransport activity, which was associated with parallel decreases in type II Na/Pi cotransporter (NaPi-2) protein and messenger RNA (mRNA) abundance. In contrast, administration of long-term physiological and supraphysiological doses of T3 resulted in significant increases in Na/Pi cotransport activity, protein, and mRNA levels. Nuclear run-on experiments indicated that thyroid hormone regulates NaPi-2 mRNA levels by a transcriptional mechanism. In aged rats, although there were no changes in T3 serum levels (when compared with young animals), there were significant decreases in serum Pi concentration, renal Na/Pi cotransport activity, and NaPi-2 protein and mRNA abundance. These effects were mediated, at least in part, by a reduction in the transcriptional rate of the NaPi-2 gene, probably caused by, among other factors, a smaller response to the stimulatory action of T3. Compared with young rats, the old rats exhibited less sensitivity of the Na/Pi cotransporter to thyroid hormone, with-decreased effects in both hypothyroid (inhibitory) and hyperthyroid (stimulatory) animals.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Absorption
  • Aging / physiology*
  • Animals
  • Biological Transport / drug effects
  • Carrier Proteins / genetics
  • Carrier Proteins / metabolism*
  • Gene Expression Regulation* / drug effects
  • Hyperthyroidism / metabolism
  • Hypothyroidism / metabolism
  • Kidney Tubules, Proximal / physiology*
  • Male
  • Phosphates / blood
  • Phosphates / metabolism*
  • RNA, Messenger / metabolism
  • Rats
  • Rats, Wistar
  • Sodium-Phosphate Cotransporter Proteins
  • Sodium-Phosphate Cotransporter Proteins, Type II
  • Symporters*
  • Thyroid Hormones / physiology*
  • Triiodothyronine / pharmacology


  • Carrier Proteins
  • Phosphates
  • RNA, Messenger
  • Sodium-Phosphate Cotransporter Proteins
  • Sodium-Phosphate Cotransporter Proteins, Type II
  • Symporters
  • Thyroid Hormones
  • Triiodothyronine