Relative increase in insulin-like growth factor I messenger ribonucleic acid levels in compensatory renal hypertrophy.

Immunoreactive insulin-like growth factor I (IGF-I) has recently been demonstrated in multiple tissues, including liver, kidney, lung, testes, and brain. Tissue IGF-I levels in hypophysectomized rats are elevated by GH. To examine whether tissue IGF-I production is regulated by local as well as systemic influences, we studied rat kidney IGF-I gene expression in renal compensatory hypertrophy occurring after unilateral nephrectomy. Northern analysis of kidney poly(A) RNA probed with [32P]IGF-I mouse cDNA revealed the presence of a mRNA species 1.3 kilobases in size. Dot hybridization of kidney poly(A) RNA showed that IGF-I mRNA was induced 5- to 6-fold in the kidneys of nephrectomized animals relative to levels in control sham-operated rats. This induction was present 24 h after surgery and continued for at least 7 days after the operation. Kidney radioimmunoassayable IGF-I content was also increased 73% in nephrectomized animals, although this was only apparent on the fourth day after surgery. In contrast, liver IGF-I mRNA levels were comparable in both experimental and control animals, suggesting that the IGF-I induction was specific to the tissue undergoing compensatory growth. Serum IGF-I and GH levels were not altered in nephrectomized and control animals for the duration of the experiments. These studies, therefore, confirm that IGF-I is synthesized in the kidney, and that kidneys undergoing compensatory growth have increased levels of IGF-I mRNA. This phenomenon occurs independently of changes in GH secretion, indicating that paracrine or autocrine factors are involved in the control of renal IGF-I production.