Effects of cytidine 5'-diphosphocholine administration on basal and growth hormone-releasing hormone-induced growth hormone secretion in elderly subjects

Abstract

The basal and GH-releasing hormone-stimulated secretion of GH declines in the elderly. We tested the ability of cytidine 5'-diphosphocholine, a drug used in the treatment of stroke and Parkinson's disease, to alter GH secretion in 11 healthy elderly volunteers, aged 69\ x=r eq-\ 84. Each subject received an iv infusion of 2 g of cytidine 5'-diphosphocholine or normal saline. GHRH and TRH were also administered during cytidine 5'diphosphocholine infusions. The infusion of cytidine 5'-diphosphocholine induced a 4-fold (p<0.05) increase in serum GH levels over basal values. A small increase in GH was seen after GHRH administration. However, the addition of GHRH to the cytidine 5'-diphosphocholine infusion resulted in a GH response which was significantly greater than that seen after GHRH alone; the integrated concentration of GH was more than 2-fold greater in the cytidine 5'-diphosphocholine treated group (706.85\m=+-\ 185.1 vs 248.9\m=+-\61.4\g=m\g \ m=. \ l \ m=-\ 1\ m=. \ (120 mi n)\m=-\1; p=0.01). The PRL and TSH responses to TRH were not significantly affected by cytidine 5'-diphosphocholine infusion, indicating that dopaminergic mechanisms are not involved. These studies demonstrate that cytidine 5'-diphosphocholine can enhance basal and GHRH-stimulated GH release in the elderly, but the mechanism of action of the drug remains unclear.Numerous studies have documented significant changes in GH secretion in aging experimental an¬ imals and in human subjects. Decreased pulsatile secretion of GH (1), a reduced ability of GHRH to release GH both in vivo and in vitro from pituitary cells in primary cultures (2), and a reduced pituitary content of GH and GH mRNA (3,4) have been reported in aged rats. Most, but not all (5), studies have confirmed that GH secretion is impaired in elderly humans. The number of sleep-related GH secretory pulses decreases in most people over 50 years of age (6,7), and there is an age-related de¬ cline in GHRH-induced GH secretion (8). The serum GH-binding protein also declines in the eld¬ erly (9).The etiology of impaired GH secretion in aging remains unclear. Alterations in the synthesis or re¬ lease of GHRH or somatostatin have been impli¬ cated, but remain unproven. Cholinergic agonists can inhibit hypothalamic somatostatin release (10) and thereby modulate GH secretion (11-13). Acti¬ vation of cholinergic receptors by the anticholinesterase pyridostigmine has been shown to restore GH responsiveness to GHRH in obese individuals (14-15) and in normal subjects (16,17). Brain acetylcholine synthesis may decline with aging (18), and it is possible that hypothalamic somatostatin tone is increased, leading to the relative hyposomatotropinemia of old age. Since dopamine stim¬ ulates GH release (19), it is also possible that de¬ creased hypothalamic dopaminergic tone could lead to decreased GH release.Cytidine 5'-diphosphocholine (CDP-choline) is a parenteral medication which has been used as a cerebral vasodilator in elderly patients (20). It has also been used in patients with stroke and Pa...

Alpha-Glycerylphosphorylcholine Administration Increases the GH Responses to GHRH of Young and Elderly Subjects

“…Since brain acetylcholine (Ach) synthesis declines with aging (Gibson, Peterson and Jenden 1981), it may be possible to restore normal GH secretion by enhancing cholinergic tone. We have recently shown that the putative Ach precursor CDP-choline is able to increase both basal and GHRH induced GH secretion in elderly human subjects (Ceda, Ceresini, Denti, Magnani, Marchini, Valenti and Hoffman 1991), lending support to the hypothesis of an increased somatostatin tone during aging.…”

Effect of choline-containing phospholipids on brain cholinergic transporters in the rat

“…GHRH is the hypothalamic hormone that triggers secretion of GH from the pituitary. The observation that both CDP-choline [49] and choline alphoscerate [50] improve the age-related decline in GH responsiveness to GHRH, further strengths the cholinergic activity of the compounds. The interference with mechanisms of GH release suggests that the two compounds may be also considered for other indications besides the most documented in cognitive domains.…”

“…In clinical pharmacology settings they counter the amnesia induced by the cholinergic muscarinic receptor antagonist scopolamine [47,48]. Moreover, CDPcholine and choline alphoscerate counter the age-related decline of both growth hormone (GH) synthesis and release [49,50]. GH decline is associated with cognitive impairment occurring in the elderly [51] and cholinergic system is an important part of mechanisms regulating GH release stimulated by growth hormone-releasing hormone (GHRH) [52].…”

Citicoline in the Treatment of Cognitive Impairment

“…Thus the effects of citicoline on the cholinergic system, together with the other actions on other neurotransmitters and its neuroprotective/neurorestorative properties, could explain the The use of citicoline in healthy adult individuals induces an increase of growth hormone secretion and a decrease on prolactin secretion [241,242].…”