STIMULATORY EFFECT OF INSULIN-LIKE GROWTH FACTOR-I ON RENAL PI TRANSPORT AND PLASMA 1,25-DIHYDROXYVITAMIN-D3

Administration of GH increases both the tubular reabsorption of inorganic phosphate (Pi) and the plasma level of 1, 25-dihydroxyvitamin D3 [l, 25-(OH)2D3]. These two effects could be induced by a common mediator, possibly the GH- generated insulin-like growth factor 1 (IGF-1). In the present work, the influence of recombinant human IGF-1 on renal Pi transport and plasma 1, 25-(OH)2D3 was examined in hypophy- sectomized (HPX) rats. IGF-1, infused by miniosmotic pump at the dose of 10 μg/h for 6 days, significantly increased the maximal tubular reabsorption of Pi per unit volume of glomerular filtrate (max TRPi/mlGFR): IGF-1 3.50 ± 0.16; vehicle: 2.78 ± 0.14 μmol/mlGFR, P < 0.005. The response was associated with a marked stimulation of plasma 1, 25-(OH)2D3 (IGF-1; 409 ± 23; vehicle: 208 ± 22 pmol/liter, P < 0.001). As previously reported for GH, IGF-1 also increased GFR and reduced urinary sodium excretion. In brush border membrane vesicles isolated from renal cortex of HPX rats, the Na-dependent Pi transport was stimulated by IGF-1. Neither the Na-dependent glucose transport nor that of alanine was affected by the growth factor. The stimulatory effect of IGF-1 on maxTRPi/mlGFR was also expressed in thyroparathyroidectomized (TPTX) HPX rats (IGF-1: 5.20 ± 0.29; vehicle: 3.88 ± 0.37 μmol/mlGFR, P < 0. 025). In conclusion, administration of IGF-1 in HPX rats mimics the stimulatory effects of GH on maxTRPi/mlGFR and on plasma 1, 25-(OH)2D3. As described for GH the change in maxTRPi/mlGFR is mediated by a PTH independent mechanism and is expressed at the level of the luminal membrane of proximal tubules. These results suggest that IGF-1 could be an important factor in the control of Pi metabolism, particularly during growth, and might play a significant role in mediating the effect of GH on the renal handling of Pi and production of 1, 25- (OH)2D3. © 1990 by The Endocrine Society.