Dietary protein restriction impairs both spontaneous and growth hormone-releasing factor-stimulated growth hormone release in the rat.

Abstract

Restriction of dietary protein stunts growth in the rat, but the mechanism is not well understood. In the present study, we examined the effects of dietary protein restriction on spontaneous and GH-releasing factor (GRF)-stimulated GH release and assessed the possible involvement of endogenous somatostatin (SRIF). Spontaneous 6-h plasma GH profiles were obtained from free-moving adult male rats fed either a 23% (normal) or 4% (low) isocaloric protein diet. Control rats exhibited the typical pulsatile pattern of GH release. In contrast, rats fed the low protein diet showed a significant reduction in GH peak amplitude (85.0 +/- 10.4 vs. 171.3 +/- 20.5 ng/ml; P < 0.01) and mean 6-h plasma GH level (18.1 +/- 2.0 vs. 40.9 +/- 6.0 ng/ml; P < 0.01) as early as 4 days after diet onset and a more than 3-fold suppression of GH pulse amplitude by 7 days. Although protein-restricted animals exhibited the typical cyclic responsiveness to 1 microgram rGRF-(1-29)NH2 i.v., the magnitude of the GH response to GRF challenge was attenuated 3- to 4-fold in these rats compared to that in normal diet-fed controls. Passive immunization of protein-restricted rats with SRIF antiserum resulted in a significant augmentation of both GH pulse amplitude (115.3 +/- 16.7 vs. 36.0 +/- 2.8 ng/ml; P < 0.01) and mean 6-h plasma GH level (34.4 +/- 5.0 vs. 10.0 +/- 1.6 ng/ml; P < 0.01) compared to those in protein-deprived rats administered normal sheep serum. Pituitary size (7.8 +/- 0.2 vs. 12.1 +/- 0.4 mg; P < 0.001) and pituitary GH content (320.5 +/- 18.9 vs. 526.6 +/- 26.8 micrograms; P < 0.001) were markedly reduced after 3-week maintenance on the 4% protein diet. In a separate study, rats fed 70% of the control diet (calorically equivalent to that consumed by rats fed 4% protein) showed no significant alteration in pulsatile GH release, thus excluding caloric restriction as a cause of the GH suppression. These results demonstrate that lack of dietary protein 1) blunts spontaneous pulsatile GH release, 2) attenuates GH responsiveness to GRF challenge, and 3) reduces pituitary GH content and size. Our findings suggest that the low protein-induced suppression of GH release is mediated at least in part by increased SRIF secretion. Such impairments in the GH neuroendocrine axis probably contribute to the growth retardation observed in this model.