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

In the present study, we have examined the cellular mechanisms mediating the regulation of renal proximal tubular sodium-coupled inorganic phosphate (Na/P-i) transport by thyroid hormone (T-3) in young and aged rats. Young hypothyroid rats showed a marked decrease in Na/P-i cotransport activity, which was associated with parallel decreases in type II Na/P-i cotransporter (NaPi-2) protein and messenger RNA (mRNA) abundance. In contrast, administration of long-term physiological and supraphysiological doses of T-3, 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 T-3 serum levels (when compared with young animals), there were significant decreases in serum P-i concentration, renal Na/P-i 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 T-3. Compared with young rats, the old rats exhibited less sensitivity of the Na/P-i cotransporter to thyroid hormone, with decreased effects in both hypothyroid (inhibitory) and hyperthyroid (stimulatory) animals.