Effects of Pyridostigmine, Corticotropin-Releasing Hormone and Growth Hormone-Releasing Hormone on the Pituitary-Adrenal Axis and on Growth Hormone Secretion in Dementia

Abstract

Alterations of neuroendocrinological indices determined by the impaired regulating effects of cholinergic neurotransmission have been described in primary dementia. In this study we have evaluated the effects of acetylcholines-terase inhibition by pyridostigmine on growth hormone (GH), adrenocorticotropic hormone (ACTH) and cortisol secretion and on their responses to GH-releasing hormone (GHRH) and corticotropin-releasing hormone (CRH) in 7 patients with primary degenerative dementia and in 8 sex- and age-matched controls. Demented subjects showed higher cortisol basal levels and lower ACTH levels than controls. Pyridostigmine increased the GH response to GHRH in both groups, the effect being significantly enhanced in patients. An increase of ACTH and cortisol levels was found in both groups after pyridostigmine and CRH administration. Pyridostigmine pretreatment significantly increased the ACTH response to CRH in controls but not in patients. The obtained data may indicate that a muscarinic receptor upregulation and an impairment of somatostatinergic function are operative in the regulation of GH secretion in dementia. An underlying hyperactivity of the hypothalamic-pituitary-adrenal axis impairs the responses of ACTH and cortisol to CRH in this disorder.

Relationship between Cognitive Function, Growth Hormone and Insulin-Like Growth Factor I Plasma Levels in Aged Subjects

“…Data on GH and IGF-I function in aging and in dementia are quite uncertain and may be influenced by methodological approach, subjects' selection, and disease severity in groups of patients with dementia [14,15].…”

“…In the present study, baseline GH and IGF-I plasma levels as well as the GH response to GHRH were evaluated in aged subjects and correlated with cognitive function. In fact, previous observations in patients with primary degenerative dementia showed that changes in spontaneous and stimulated GH secretion were related to disease severity and to memory alterations [14,15].…”

Post-poliomyelitis syndrome

“…It was hypothesized that pyridostigmine would improve fatigue by repairing defective neuromuscular transmission. Pyridostigmine may also have more chronic, trophic effects mediated through GH and IGF‐149, 89, 91 and other factors 33, 123. Neuromuscular transmission can improve with anticholinesterases in post‐polio patients 60, 134.…”

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.…”