Long-Term Alterations in Growth Hormone and Insulin Secretion after Temporary Dietary Protein Restriction in Early Life in the Rat

Abstract

Protein malnutrition early in life stunts subsequent physical growth in both humans and rats, but the mechanism(s) is unknown . To test the hypothesis that temporary early life dietary protein restriction produces long-term alterations in the grow th hormone (GH) neuroendocrine axis, we examined the effects of 3 wk of exposure to dietary protein restriction in male rats postwea ning (3-6 wk of age) on spontaneous and GH-releasing factor (GRF)-stimulated GH secretion at 12 wk of age. In compar ison to rats weaned onto a normal diet (23% protein), rats weaned onto a low (4%) protein diet failed to catch up growth when transferred to the normal diet between 6 and 12 wk of age. Spontaneous 6-h GH secretory profiles of adult rats fed the low protein diet early in life showed a 41% reduction in mean GH peak amplitude and a significant suppression in overall mean 6-h plasma GH concentra tions (37.5 ± 4.5 versus 56.9 ± 5.9 J.Lg/L; p < 0.02). The magnitude of the GH response to 1 J.Lg of rat GRF(I-29)NH 2 i.v. challenge was augmented during the GH trough period in these rats (165.7 ± 30.4 versus 43.9 ± 17.6 J.Lg/L; P < 0.01). Although basal plasma lGF-l levels and glucose tolerance of protein-deprived rats were normal at 12 wk of age, the insulin response to ip glucose was severely blunted [insulin Undernutrition in early life impairs subsequent physical growth in both humans (1-4) and rats (5), but the mechanism (s) is not yet known. Exposure to early postnatal undernutrition, in genera l, and protein malnutritio n, in particular, has deleterious effects on the development and func tion of various organs, and leads to lower protein/DNA ratios in several tissues (5-10). Such persisting cellular hypoplasia may result in insufficient cellular machi nery for hormonal biosynthesis.

Energy restriction with protein restriction increases basal metabolism and meal-induced thermogenesis in rats

“…In the latter study, the absence of significant change could be explained by the fact that the meals were tube fed, a procedure that shunts orosensory responses to a meal (18,21) and thus attenuates the sympathetic response to feeding. The elevated mealinduced thermogenesis seen in our study may have resulted from a higher insulin activity in peripheral tissues (13,24), leading to increased rates of glucose oxidation during the postprandial period and then to increased BAT activation.…”

Alteration of the counterregulatory hormones in the conscious rat after protein-energy restriction

“…Of course this possibility is not exclusive and there are several other possible mechanisms to explain the alpha-cell increased response in the restricted rats: basal alpha-cell hyperfunction could be caused by the direct effect of the low basal glucose level, and/or a decrease in the islet concentration of insulin and/or g -aminobutyric acid (GABA), two agents which are potent inhibitors of glucagon release [29]. The finding of normal pancreatic somatostatin (SRIF) concentration in a similar protein-restricted rat model suggests that intrapancreatic SRIF is not involved in the enhanced alpha-cell response [30].…”

“…Of course additional studies are warranted to test this hypothesis, but there are indications in the literature that protein deprivation significantly impairs a variety of neurotransmitter systems in the CNS including b -endorphin [45], norepinephrine [46], neuropeptide Y [47] and growth hormone-releasing factor (GRF) [48]. Concerning this last neuropeptide, it has been proposed that a reduction in hypothalamic GRF signalling to pituitary somatotrophs after dietary protein restriction is a major determinant of the suppression of the pulsatile growth hormone secretion [30,49], with a resulting decreased basal plasma growth hormone level as confirmed in our present study.…”

Birth Weight and Weight at 1 Year Are Independent Determinants of Bone Mass in the Seventh Decade: The Hertfordshire Cohort Study

“…We have previously reported associations between weight at 1 y of age and circulating GH concentration in an older Hertfordshire cohort (25), and indeed there is evidence from animal models that the pattern of GH concentration in adult life may be influenced by transient 585 EARLY LIFE AND BONE MASS IN HERTFORDSHIRE events in early postnatal life, including temporary dietary protein restriction in rats after weaning (26). Similarly, Bishop et al (27) demonstrated higher BMC at a 5-y follow-up in preterm infants who were previously randomly assigned to human milk versus formula.…”