HORMONAL-CONTROL OF GROWTH IN THE GENETICALLY-OBESE ZUCKER RAT .1. LINEAR GROWTH, PLASMA INSULIN-LIKE GROWTH FACTOR-I (IGP-I) AND IGF-BINDING PROTEINS

The genetically obese Zucker rat is a widely used model of early-onset obesity. Like obese children, these obese rats are hyperinsulinemic and have low GH secretion. However, data on linear growth and insulin-like growth factor-I (IGF-I) levels in this model are scanty and contradictory. In the present study, we investigated linear growth and its hormonal control in Zucker rats (male and female) from 4-20 weeks of age. In the obese animals, compared to their lean littermates, the naso-anal length was normal or slightly greater, whereas the tails and femurs were shorter. The plasma concentration of IGF-I increased between 4-20 weeks of age, and IGF-I levels were normal or slightly higher in the obese animals. The serum level of IGF-binding protein-3 (IGFBP-3) measured by Western ligand blotting was not significantly different in lean vs, obese rats. To assess the IGF-I response to GH, bovine GH was administered (250 mu g/100 g BW, ip, daily for 3 days) to 16- to 20-week-old female Zucker rats; plasma IGF-I concentrations increased more in the obese (percent increase over baseline, 347 +/- 44% vs. 194 +/- 31%; P < 0.01). These results show that despite low GH secretion, genetically obese Zucker rats have 1) normal linear (nasoanal) growth, 2) normal or increased circulating levels of IGF-I and IGFBP-3, and 3) increased plasma IGF-I responses to exogenous GH. These results suggest that the GH-independent growth in this model could result from direct effects of hyperinsulinism on circulating IGF-I and IGFBP-3 levels and/or indirect effects through increased GH receptor function.