Young male rats subjected to a dietary manganese (Mn) deficiency respond to the deficiency by reducing their growth rate. The growth hormone (GH)/insulin-like growth factor (IGF) axis is critical for linear growth; this system is exquisitely sensitive to the nutritional state of the animal. In this study, we examined circulating GH, IGF-1, and insulin levels in Mn-deficient (−Mn; fed a 0.5 μg Mn/g diet) and sufficient (+Mn; fed a 45 μg Mn/g diet) male Sprague-Dawley rats. Additionally, we examined the distribution of circulating IGF binding proteins (IGFBPs) in animals of both dietary groups as these proteins modulate IGF-1 action in vivo and in vitro, and have been demonstrated to be altered in a number of nutritional and physiological states.
Body weight was significantly reduced in −Mn relative to +Mn rats. Consistent with other studies, daily food intake was not altered. However, cumulative food intake (over 3 months) was marginally lower in −Mn versus +Mn animals. −Mn animals displayed lower circulating concentrations of IGF-1 (66% of control levels) and insulin (60% of control levels) despite having significant elevations in circulating GH levels relative to +Mn animals (140% of control levels). The IGFBP profile of −Mn animals reflected their elevated GH status, as we observed increased binding of tracer (125I-IGF-1) to the circulating IGFBP-3 complex (120% of control binding) using native chromatography techniques. Interestingly, the lower circulating insulin concentrations of −Mn animals did not result in dramatic elevations in lower-molecular-weight binding proteins.
In summary, we demonstrate that in young male rats, Mn deficiency is associated with alterations in IGF metabolism. These alterations may contribute to the growth and bone abnormalities observed in −Mn animals.