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.
Chin
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Developmental Endocrinology Branch, National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, Maryland 20892.
Bondy
C A
CA
D000818:Animals; D001835:Body Weight / Q000187:drug effects; D002352:Carrier Proteins / Q000235:genetics; D004044:Dietary Proteins / Q000494:pharmacology*; D015870:Gene Expression; D013006:Growth Hormone / Q000172:deficiency; D006965:Hyperplasia; D018970:Insulin-Like Growth Factor Binding Protein 1; D007334:Insulin-Like Growth Factor I / Q000096:biosynthesis* / Q000235:genetics; D007668:Kidney / Q000254:growth & development* / Q000378:metabolism* / Q000473:pathology; D009929:Organ Size / Q000187:drug effects; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D011910:Rats, Brattleboro; D011922:Rats, Mutant Strains; D017207:Rats, Sprague-Dawley; D013002:Somatomedins / Q000096:biosynthesis; D014667:Vasopressins / Q000172:deficiency
D002352:Carrier Proteins; D004044:Dietary Proteins; D018970:Insulin-Like Growth Factor Binding Protein 1; D012333:RNA, Messenger; D013002:Somatomedins; D014667:Vasopressins; D007334:Insulin-Like Growth Factor I; D013006:Growth Hormone