Cholinergic Modulation of Growth Hormone-Releasing Hormone Effects on Growth Hormone Secretion in Dementia

Abstract

An impairment of cholinergic and somatostatinergic neurotransmission have been reported in dementia. Both acetylcholine and somatostatin are involved in the regulation of growth hormone (GH) secretion. The effects of GH-releasing hormone (GHRH) 1–44 on GH release have been studied before and after the pretreatment with pyridostigmine or pirenzepine in subjects with senile dementia of the Alzheimer type, multi-infarct dementia and mixed dementia. The data have been compared with those obtained in an age-matched healthy control group. The GH response to GHRH is similar in the patients and in the controls, though the peak occurrence is significantly delayed in dementia. The cholinesterase inhibitor pyridostigmine enhances significantly the GH response to GHRH in both groups. The responses obtained in demented subjects are significantly larger than those found in the controls. Pirenzepine, a muscarinic receptor blocker, inhibits the GHRH effect on GH secretion in both groups. The findings may be interpreted in terms of an underlying impairment of the hypothalamic cholinergic neurotransmission, with an acetylcholine receptor supersensitivity that becomes apparent when the cholinergic tonus is enhanced by the inhibition of cholinesterase by pyridostigmine. No significant differences, due to the type of dementia, have been observed.

Growth Hormone Secretion in Alzheimer's Disease: Studies with Growth Hormone-Releasing Hormone Alone and Combined with Pyridostigmine or Arginine

“…Four out of 15 patients studied by us had early-onset disease and a clear GH response to all stimuli, but this pattern was also observed in older patients with late-onset disease. Moreover, in contrast to others [16,17], we did not find any delay in somatotroph responsiveness to GHRH alone or combined with PD or ARG in AD.…”

“…Previous studies [15][16][17] showed no difference in the magnitude of the GHRHinduced GH release between AD patients and agematched controls.…”

“…On the other hand, the enhancement of the cholinergic activity by pyridostig mine when given alone (present data) as well as by edro phonium [19] has the same stimulating effect on GH secretion in normal elderly subjects and in demented patients. An increase in the GHRH-induced GH release after pretreatment with PD in demented patients has been reported recently [17], It is widely accepted that GH secretion declines with age in humans [20][21][22] so that normal elderly subjects have GH and IGF-I levels similar to those of patients with GH deficiency [20,21], In patients with AD basal GH levels similar [15,23, 24] or higher [23] than those in agematched normal elderly subjects have been reported. Moreover, in AD, IGF-I concentrations have been found to be low, but higher than those recorded in age-matched controls [25,26].…”

Human Ageing and the Growth Hormone/Insulin-Like Growth Factor-I (GH/IGF-I) Axis - The Impact of Growth Factors on Dementia

“…Indeed, cholinergic agonists are able to increase both spontaneous and GHRH-induced GH secretion in AD patients [142,[152][153][154]156] without any difference with normal elderly [142,153], although both responses are reduced compared with normal young subjects [142]. These findings, therefore, confirmed the presence of neuroendocrine cholinergic derangement in the ageing brain but demonstrated that, at least at hypothalamic level, cholinergic pathways are not more impaired in AD than in normal elderly.…”

“…On the other hand, other studies focusing on the effects of other neuroactive drugs able to stimulate GH secretion, such as clonidine, pyridostigmine and apomorphine, generally confirmed that AD shows a GH response similar to that in normal elderly subjects [141,142,[152][153][154][155][156].…”