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 th e regulation of renal proximal tubular sodium-coupled inorganic phosphate ( Na/P-i) transport by thyroid hormone (T-3) in young and aged rats. Young hy pothyroid rats showed a marked decrease in Na/P-i cotransport activity, whi ch was associated with parallel decreases in type II Na/P-i cotransporter ( NaPi-2) protein and messenger RNA (mRNA) abundance. In contrast, administra tion of long-term physiological and supraphysiological doses of T-3, result ed in significant increases in Na/Pi cotransport activity, protein, and mRN A levels. Nuclear run-on experiments indicated that thyroid hormone regulat es NaPi-2 mRNA levels by a transcriptional mechanism. In aged rats, althoug h there were no changes in T-3 serum levels (when compared with young anima ls), there were significant decreases in serum P-i concentration, renal Na/ P-i cotransport activity, and NaPi-2 protein and mRNA abundance. These effe cts 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 o ld rats exhibited less sensitivity of the Na/P-i cotransporter to thyroid h ormone, with decreased effects in both hypothyroid (inhibitory) and hyperth yroid (stimulatory) animals.