CIRCULATING AND SKELETAL INSULIN-LIKE GROWTH-FACTOR-I (IGF-I) CONCENTRATIONS IN 2 INBRED STRAINS OF MICE WITH DIFFERENT BONE-MINERAL-DENSITIES

Recent work has demonstrated differences in femoral bone mineral densi ty between two common inbred strains of mice, C3H/HeJ (C3H) and C57BL/ 6J (B6), across a wide age range. To investigate one possible mechanis m that could affect acquisition and maintenance of bone mass in mice, we studied circulatory and skeletal insulin-like growth factor-I (IGF- I) and femoral bone mineral density (F-BMD) by pQCT in C3H and B6 prog enitor strains, as well as serum IGF-I obtained from matings between t hese two strains and mice bred from subsequent F-1 intercrosses (F-2). Serum IGF-I measured by radioimmunoassay was more than 35% higher in virgin progenitor C3H than virgin B6 at 1, 4, 8, and 10 months of age, and in 8-month-old C3H compared with B6 retired breeders (p < 0.001). In the progenitors, there was also a strong correlation between serum IGF-I and serum alkaline phosphatase (r = 0.51,p = 0.001). In the 4 m onth F-1 females IGF-I levels and F-BMD were intermediate between C3H and B6 progenitors. In contrast, groups of F-2 mice with the highest o r lowest BMD also had the highest or lowest serum IGF-I (p = 0.0001). IGF-I accounted for >35% of the variance in F-BMD among the F-2 mice. Conditioned media from newborn C3H calvarial cultures had higher conce ntrations of IGF-I than media from B6 cultures, and cell layer extract s from C3H calvariae exhibited greater alkaline phosphatase activity t han cultures from B6 calvarial cells (p < 0.0001). The skeletal conten t of IGF-I in C3H tibiae, femorae, and calvariae (6-14 weeks of age) w as also significantly higher than IGF-I content in the same bones of t he B6 mice (p < 0.05). These data suggest that a possible mechanism fo r the difference in acquisition and maintenance of bone mass between t hese two inbred strains is related to systemic and skeletal IGF-I synt hesis. (C) 1997 by Elsevier Science Inc. All rights reserved.