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 respo nse to elevated dietary protein. In the present study, rats were fed i socaloric diets containing variable protein content (6-40%) for 1-7 da ys, and changes in fractional renal weight, MTAL length, and regional DNA synthesis were assayed and compared with local changes in IGF-I/IG FBP-1 mRNAs, as determined by quantitative in situ hybridization. Rats switched to high-protein diets demonstrated increased IGF-I and decre ased IGFBP-1 mRNA levels in MTALs, whereas those switched to low prote in showed inverse changes. The increase in renal IGF-I mRNA was maxima l at 2 days and was closely paralleled by significant increases in fra ctional 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 tha t the effects of dietary protein in this model are not mediated by vas opressin or GH. The close spatial and temporal correlation between cha nges in renal IGF-I expression and changes in regional growth paramete rs strongly supports a role for locally produced IGF-I in the inductio n of protein-induced renal growth.