THE INFLUENCE OF MANGANESE DEFICIENCY ON SERUM IGF-1 AND IGF BINDING-PROTEINS IN THE MALE-RAT

Young male rats subjected to a dietary manganese (Mn) deficiency respo nd to the deficiency by reducing their growth rate. The growth hormone (GH)/insulin-like growth factor (IGF) axis is critical for linear gro wth; this system is exquisitely sensitive to the nutritional state of the animal, In this study, we examined circulating GH, IGF-1, and insu lin levels in Mn-deficient (-Mn; fed a 0.5 mu g Mn/g diet) and suffici ent (+Mn; fed a 45 mu g Mn/g diet) male Sprague-Dawley rats. Additiona lly, 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 al tered in a number of nutritional and physiological states. Body weight was significantly reduced in -Mn relative to +Mn rats. Consistent wit h other studies, daily food intake was not altered. However, cumulativ e food intake (over 3 months) was marginally lower in -Mn versus +Mn a nimals. -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 re flected their elevated GH status, as we observed increased binding of tracer (I-125-IGF-1) to the circulating IGFBP-3 complex (120% of contr ol binding) using native chromatography techniques, Interestingly, the lower circulating insulin concentrations of -Mn animals did not resul t in dramatic elevations in lower-molecular-weight binding proteins. I n summary, we demonstrate that in young male rats, Mn deficiency is as sociated with alterations in IGF metabolism. These alterations may con tribute to the growth and bone abnormalities observed in -Mn animals.