Growth-Hormone Secretion In Alzheimers-Disease - Studies With Growth Hormone-Releasing Hormone Alone And Combined With Pyridostigmine Or Arginine

There is evidence that GH secretion is reduced in normal elderly subjects as well as in patients with Alzheimer's disease (AD). To clarify the mechanisms underlying this GH hyposecretory state in 14 elderly subjects (age 65-75 years) and 15 AD patients (age 61-78 years), we studied the effects of both pyridostigmine (PD, 120 mg orally), a cholinesterase inhibitor, and arginine (ARG, 0.5 g/kg i.v.), two substances likely acting via inhibition of hypothalamic somatostatin, on GH response to GHRH (1 mu g/kg i.v.). The GH response to PD alone was also studied. Twenty-two young healthy volunteers were studied as control group. Basal GH levels were similar in young, elderly and AD subjects (0.7 +/- 0.2, 0.8 +/- 0.2 and 0.9 +/- 0.2 mu g/l). IGF-I levels were lower (p < 0.005) in elderly (73.9 +/- 8.2 mu g/l) and in AD subjects (108.0 +/- 5.9 mu g/l) than in young subjects (288.7 +/- 22.1 mu g/l); however, they were higher (p < 0.01) in AD patients than in the elderly subjects. The PD-induced GH release did not significantly differ in young, elderly and AD subjects while the GH responses to GHRH in the elderly (AUC: 297.9 +/- 49.2 mu g/l/h) and in AD subjects (437.6 +/- 93.5 mu g/l/h) were lower (p < 0.01) than in young subjects (658.6 +/- 100.1 mu g/l/h). PD potentiated the CH response to GHRH both in elderly and in AD subjects (901.7 +/- 222.4 and 1,070.3 +/- 207.2 mu g/l/h, p < 0.005) but these responses were lower (p < 0.0001) than those recorded in young subjects (2,041.1 +/- 245.6 mu g/l/h). ARG potentiated the GHRH-induced GH rise both in elderly and in AD subjects(1,545.2 +/- 246.0 and 1,659.3 +/- 196.8 mu g/l/h, p < 0.001) but in this case, the GH response to GHRH + ARG overlapped with that in young subjects(2,140.2 +/- 229.5 mu g/l/h). In contrast to young subjects, in elderly and in AD subjects, the potentiating effect of ARG on GHRH-induced GH rise was higher (p < 0.01) than that of PD. These results show that testing neural controls of GH secretion with different neuroactive substances does not allow to differentiate normal aging from AD. In both groups, somatotroph responsiveness to GHRH is potentiated by the enhancement of the cholinergic activity but much more by ARG, which is compatible with the presence of a cholinergic impairment.