Effect of fetal nephrectomy on insulin-like growth factors and their binding proteins in sheep

Bilateral nephrectomy retards fetal growth and decreases somatomedin (insulin-like growth factor-I, IGF-I) activity. To determine whether nephrectomy alters the synthesis of IGF-I or its binding proteins (IGFBPs), we studied 6 sets of twin fetuses. Kidneys were removed bilaterally from 1 twin of each set at 112-122 days of gestation (term 145 days). Plasma IGF-I concentrations were greater in nephrectomized fetuses than in the intact twins during the 1st week (261 +/- 35 vs. 153 +/- 21 ng/ml, p < 0.02; mean +/- SE) but not the 2nd week after surgery. Nephrectomy increased the abundance of the IGFBPs to levels 2-3 times greater than those in intact twins. Fetal hepatic IGFBP1 mRNA levels increased in 4 of 6 nephrectomized fetuses, while those of IGF-I, IGF-II, IGFBP2 were unchanged. Nephrectomy markedly alters the abundance of IGF-I and IGFBPs in plasma probably through mechanisms unrelated to synthesis.