Altered expression of insulin-like growth factor-I (IGF-I) and IGF receptor genes after unilateral nephrectomy in immature rats.

There is a developmental difference in the initial phase of compensatory renal growth (CRG) following unilateral nephrectomy (UNX), in that CRG is GH-dependent in adult rats and GH-independent in immature rats. Furthermore, CRG in immature rats is associated with an increase in renal IGF-I mRNA, an effect not seen in adult rats. In this study we have examined the age-related differences in expression of the insulin-like growth factor-I (IGF-I) and IGF-II genes as well as in IGF-I and IGF-II receptors and membrane binding after UNX. Immature (22-24 days of age) and adult (4 months of age) male Wistar rats underwent a sham operation or left UNX and were killed 24 or 48 h later. Levels of mRNA for IGF-I and IGF-II and their receptors were determined in the left (control) and right (compensated) remnant kidneys using solution hybridization/RNase protection assays. Steady state levels of IGF-I mRNA as well as IGF-I receptor and IGF-II/mannose-6-phosphate receptor mRNAs were increased 3- to 4-fold in immature remnant kidneys, but not in adult kidneys. The findings related to IGF-I gene expression were confirmed by in situ hybridization to immature and adult kidney slices. The increase in IGF-I gene expression in the immature remnant kidneys was localized to the thick ascending limbs of the loops of Henle. Furthermore, in concert with the changes in mRNA levels, membrane binding studies showed significant increases in specific binding to IGF-I in cortical membranes and increases in specific binding to IGF-II in whole kidney membranes from immature, but not adult, rats. Thus, these findings demonstrate that the initial phase of CRG in the immature rat is associated with increased renal IGF-I gene expression as well as enhanced specific renal binding of IGF-I and IGF-II to plasma membranes and support the notion that this period of rapid renal growth in the immature UNX rat may involve the paracrine influence of the IGFs.