DIETARY-PROTEIN RESTRICTION IMPAIRS BOTH SPONTANEOUS AND GROWTH HORMONE-RELEASING FACTOR-STIMULATED GROWTH-HORMONE RELEASE IN THE RAT

Restriction of diet protein stunts growth in the rat, but the mechanis m is not well understood. In the present study, we examined the effect s of dietary protein restriction on spontaneous and GH-releasing facto r (GRF)-stimulated GH release and assessed the possible involvement of endopnous somatostatin (SREF). Spontaneous 6-h plasma GH profiles wer e obtained from free-moving adult male rats fed either a 23% (normal) or 4% (low) isocaloric protein diet. Control rats exhibited the typica l pulsatile pattern of GH release. In contrast, rats fed the low prote in 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 v8. 40.9 +/- 6.0 ng/ml; P < 0.01) as early as 4 days aft er 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 mug rGRF-(1-29)NH2 iv, the magnitude of the GH response to GRF challenge was attenuated 3- to 4-fold in these rat a compared to that in normal diet-fed controls. Passive immunization o f protein-restricted rats with SREF antiserum resulted in a significan t 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. 1 0.0 +/- 1.6 ng/ml; P < 0.01) compared to those in protein-deprived rat s 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 mug, P < 0.001) were markedly after 3-week maintenance on the 4% protein diet. In a separate study, rats fed 70% of the contr ol diet (calorically equivalent to that consumed by rats fed 4% protei n) showed no significant alteration in pulsatile GH release, thus excl uding caloric restriction as a cause of the GH suppression. These resu lts demonstrate that lack of dietary protein 1) blunto spontaneous pul satile GH release, 2) attenuates GH responsiveness to GRF challenge, a nd 3) reduces pituitary GH content and size. Our findings suggest that the low protein-induced suppression of GH release is mediated at leas t in part by increased SRIF secretion. Such impairments in the GH neur oendocrine axis probably contribute to the growth retardation observed in this model.