Dietary protein-induced renal growth: correlation between renal IGF-I synthesis and hyperplasia

Insulin-like growth factor I (IGF-I) and IGF binding protein 1 (IGFBP-1) mRNAs are colocalized in the medullary thick ascending limb (MTAL) of the rat nephron, a segment that undergoes selective growth in response to elevated dietary protein. In the present study, rats were fed isocaloric diets containing variable protein content (6-40%) for 1-7 days, and changes in fractional renal weight, MTAL length, and regional DNA synthesis were assayed and compared with local changes in IGF-I/IGFBP-1 mRNAs, as determined by quantitative in situ hybridization. Rats switched to high-protein diets demonstrated increased IGF-I and decreased IGFBP-1 mRNA levels in MTALs, whereas those switched to low protein showed inverse changes. The increase in renal IGF-I mRNA was maximal at 2 days and was closely paralleled by significant increases in fractional renal weight, DNA synthesis, and MTAL length. Similar changes were seen in vasopressin-deficient Brattleboro and growth hormone (GH)-deficient dwarf rats in response to high-protein diets, suggesting that the effects of dietary protein in this model are not mediated by vasopressin or GH. The close spatial and temporal correlation between changes in renal IGF-I expression and changes in regional growth parameters strongly supports a role for locally produced IGF-I in the induction of protein-induced renal growth.