EFFECT OF 15-DAY TREATMENT WITH GROWTH-HORMONE-RELEASING HORMONE ALONE OR COMBINED WITH DIFFERENT DOSES OF ARGININE ON THE REDUCED SOMATOTROPE RESPONSIVENESS TO THE NEUROHORMONE IN NORMAL AGING

It is well known that both spontaneous and growth hormone-releasing hormone (GHRH)-stimulated GH secretion undergo an age-related decrease; in addition, there is supportive evidence that the GH hyposecretory state of aging is of hypothalamic origin. The aims of the study in 35 normal elderly subjects (20 males and 15 females aged 65-89 years) were to verify whether the low somatotrope responsiveness to GHRH (1 mu g/kg) can be primed by a daily GHRH treatment and whether the potentiating effect of both high intravenous (0.5 g/kg) and low oral (8 g) doses of arginine (ARG) on GH response to GHRH is maintained with time. In group A (N = 14) the GH response to GHRH on day 1 (AUC: 373.5 +/- 78.5 mu g.l(-1).h(-1)) was unchanged after 7 (3720 +/- 38 mu g.l(-1).h(-1)) and 15 days (377.9 +/- 63.8 mu g.l(-1).h(-1)) of daily GHRH administration, In group B (N = 6) the GH response to GHRH co-administered with iv ARG on day 1 (1614.2 +/- 146.2 mu g.l(-1).h(-1)) was higher (p < 0.05) than that of GHRH alone (group A) and persisted unchanged after 7 (1514.7 +/- 366.5 mu g.l(-1).h(-1)) and 15 days (1631.7 +/- 379.1 mu g.l(-1).h(-1)) of treatment, In group C (N 15) the GH response to GHRH co-administered with oral ARG on day 1 (950.6 +/- 219.4 mu g.l(-1).h(-1)) was higher (p < 0.03) than that of GHRH alone (group A) but lower (p < 0.05) than that to GHRH plus iv ARG (group B). It was unchanged after 7 (816.2 +/- 208.5 mu g.l(-1).h(-1)) and 15 days (760.4 +/- 165.0 mu g.l(-1).h(-1)) of treatment; these responses were still higher (p < 0.05) than that to GHRH alone. Insulin-like growth factor I levels were not modified by any of the treatments. In conclusion, our results demonstrate that in normal aging the low somatotrope responsiveness to GHRH is not improved by prolonged treatment with the neurohormone but it is enhanced by the combined treatment with ARG and this effect does not vanish after a 15-day treatment period. The effect of ARG is present even after a low oral dose, although less markedly than after a high intravenous dose.