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 growth hormone (GH) neuroendocrine axis, we examined the effects of 3 wk of exposure to dietary protein restriction in male rats postweaning (3-6 wk of age) on spontaneous and GH-releasing factor (GRF)-stimulated GH secretion at 12 wk of age. In comparison 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 concentrations (37.5 +/- 4.5 versus 56.9 +/- 5.9 micrograms/L; p < 0.02). The magnitude of the GH response to 1 microgram of rat GRF(1-29)NH2 i.v. challenge was augmented during the GH trough period in these rats (165.7 +/- 30.4 versus 43.9 +/- 17.6 micrograms/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 response 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 early in life 1) blunts spontaneous pulsatile GH secretion, 2) augments GH responsiveness to GRF challenge, and 3) reduces the insulin secretory 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 sensitivity to glucose. Such alterations in the GH neuroendocrine axis, together with the subnormal insulin secretion, likely contribute to the lack of catch-up growth in this model.