Reduction of Serum Insulin-like Growth Factor-I by Dietary Protein Restriction Is Age Dependent

Abstract

ABSTRACT. We have determined if dietary protein restriction for 1 wk has differential effects on growth, serum IGF-I, and liver growth hormone receptors at various stages of development. Female Wistar rats were fed a low (5%) protein diet for 7 d at 3, 4, 6, 8, and 12 wk of age, whereas controls were maintained on a normal (15%) protein diet. Body wt gain was impaired in the groups fed the low protein diet, despite normal energy intake, and the effect was attenuated with age. Liver cell number (DNA content) was reduced by low protein feeding in the 3-, 4-, and 6-wk age groups ( p < 0.01), but not in the older animals. Protein restriction caused a dramatic decrease in serum IGF-I in the younger animals (90 and 82% reduction versus normal fed age-matched controls, at 3 and 4 wk, respectively; p < 0.001), and this effect was progressively attenuated with increasing age (49,40, and 25% reductions of serum IGF-I at 6, 8, and 12 wk, respectively). Changes in serum IGF-I correlated with those of liver cell number (r = 0.80; p < 0.001). Total and free liver growth hormone receptors were slightly decreased in the low protein diet groups at 4 ( p c 0.05) and 6 wk (total: p < 0.001; free: p < 0.01) but not in the other age groups. The occurrence of profound diet induced reductions in IGF-I without proportional reductions in liver GH receptors suggest that the apparent GH resistance occurs at a postreceptor level. Because the degree of IGF-I reduction correlates with the severity of retardation of liver growth during dietary protein restriction at different ages, we conclude that the effect of protein restriction on liver growth could be mediated through IGF-I. (Pediatr Res 26: 415-419, 1989) Abbreviations rGH, rat growth hormone bGH, bovine growth hormone ANOVA, analysis of variance The GH-dependent peptide IGF-I is widely believed to be one of the principal stimulators of the cell proliferation that results in somatic growth (1). Regulated by food intake and nutritional

Caloric restriction: Impact upon pituitary function and reproduction

“…It seems that both GH and one if its peripheral mediators of function, insulin-like growth factor-1 (IGF-1) are both implicated in the growth retardation associated with chronic caloric restriction (Harel and Tannenbaum, 1993). Protein restriction in animal models reduces circulating levels of IGF-1 (Fliesen et al, 1989) and also increases IGF-1 clearance from circulation (Thissen et al, 1992). Recovery of growth retardation in such animals though is not achieved with simple IGF-1 replacement, which demonstrates that disruption of GH pulsatility through CR is probably the prime mediator of the growth effects.…”

Adaptation of the growth hormone and insulin-like growth factor-I axis to chronic and severe calorie or protein malnutrition.

“…While these studies describe nutritional influences on the axis, most were limited to pubertal animals studied for a few days and did not control for equivalent micronutrient intake when deficient macronutrient diets were prepared. One report demonstrates that protein deficiency in the weanling rat reduces serum IGF-I significantly more than in the adult rat (24). This suggests a reduction in IGF-I sensitivity to protein deficiency with age.…”

Papel de la proteína supresora de la señalización por citocinas-3 (SOCS 3) en la resistencia a la hormona de crecimiento inducida por malnutrición.

“…En el presente trabajo se encontró que, además del descenso en los niveles de IGF-I circulante, la restricción disminuyó de manera significativa el contenido de ARNm del receptor y el número de sitios de enlace a GH en el hígado. Se ha descrito que restricciones durante períodos más cortos al empleado en el presente estudio no alteran la capacidad de unión a GH a pesar de los niveles disminuidos del receptor (28,29).…”