Effect of thyroxine administration on phosphate transport across renal cortical brush border membrane

Previous studies indicate that in hyperthyroid states the renal tubular reabsorption of phosphate is enhanced. To determine the cellular basis of this phenomenon, we investigated the effect of L-thyroxine (T₄) administration on P(i) transport across brush border membrane vesicles (BBMV) from rat renal cortex. Rats were thyroparathyroidectomized, fed a diet containing 1.2% phosphate, and treated intraperitoneally for 6 days with 200 μg T₄·100 g body wt^-1·day^-1. At the end of the treatment period, the rats had a significantly (+Δ 25%) elevated plasma P(i) and a slightly decreased plasma Ca compared with controls. The renal clearance of P(i) was not different between the two groups. Na⁺ gradient-dependent uptake of ³²P(i) by BBMV from renal cortex was significantly enhanced in T₄-treated rats. BBMV uptake of ³²P(i) in the absence of Na⁺-gradient as well as Na⁺ gradient-dependent uptake of D-[³H]glucose and L-[³H]proline did not differ between BBMV from T₄-treated and control rats. Kinetic analysis showed that the Na⁺ gradient-dependent uptake ³²P(i) transport system in BBMV from T₄-treated had a significantly increased V(max) compared with controls (5.2 ± 0.4 vs. 4.1 ± 0.4 nmol P(i)·30s^-1·mg protein^-1) and also a slightly higher affinity for P(i) (apparent K(m) in controls, 95 ± 9; in T₄-treated, 78 ± 8 μM). Gluconeogenesis in cortical slices was not significantly different between T₄-treated rats and controls. Specific activities of alkaline phosphatase and γ-glutamyltransferase were significantly lower in BBMV from the T₄-treated group compared with controls. We conclude that T₄ administration increased the Na⁺ gradient-dependent P(i) uptake in BBMV and that this phenomenon may be, at least in part, the cellular basis for the enhanced proximal tubular reabsorption of P(i) elicited by T₄ administration or observed in hyperthyroid states.