LONG-TERM ALTERATIONS IN GROWTH-HORMONE AND INSULIN-SECRETION AFTER TEMPORARY DIETARY-PROTEIN RESTRICTION IN EARLY-LIFE IN THE RAT

Protein malnutrition early in life stunts subsequent physical growth i n both humans and rats, but the mechanism(s) is un known. To test the hypothesis that temporary early life dietary protein restriction produ ces long-term alterations in the growth hormone (GH) neuroendocrine ax is, we examined the effects of 3 wk of exposure to dietary protein res triction in male rats postweaning (3-6 wk of age) on spontaneous and G H-releasing factor (GRF)-stimulated GH secretion at 12 wk of age. In c omparison to rats weaned onto a normal diet (23% protein), rats weaned onto a low (4%) protein diet failed to catch up growth transferred to the normal diet between 6 and 12 wk of age. Spontaneous 6-h GH secret ory profiles of adult rats fed the low protein diet early in life show ed a 41% reduction in mean GH peak amplitude and a significant suppres sion in overall mean 6-h plasma GH concentrations (37.5 +/- 4.5 versus 56.9 +/- 5.9 mu g/L; p < 0.02). The magnitude of the GH response to 1 mu g of rat GRF(1-2 )NH2 i.v. challenge was augmented during the GH t rough period in these rats (165.7 +/- 30.4 versus 43.9 +/- 17.6 mu g/L ; P < 0.01). Although basal plasma IGF-I levels and glucose tolerance of protein-deprived rats were normal at 12 wk of age, the insulin resp onse to ip glucose was severely blunted [insulin integrated area under the curve: 303.0 +/- 32.7 versus 778.3 +/- 105.0 pmol/L/75 min; p < 0 .01]. These results demonstrate that temporary protein malnutrition ea rly in life 1) blunts spontaneous pulsatile GH secretion, 2) augments GH responsiveness to GRF challenge, and 3) reduces the insulin secreto ry response to glucose in adulthood. Our findings suggest that dietary protein in early life is an important determinant for CNS control of GH secretion as well as for the development of pancreatic beta-cell se nsitivity to glucose. Such alterations in the GH neuroendocrine axis, together with the subnormal insulin secretion, likely contribute to th e lack of catch-up growth in this model.