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

1991 ◽  
Vol 124 (5) ◽  
pp. 516-520 ◽  
Author(s):  
Gian Paolo Ceda ◽  
Graziano Ceresini ◽  
Licia Denti ◽  
Dario Magnani ◽  
Lorenzo Marchini ◽  
...  

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 69-84. 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± 185.1 vs 248.9±61.4 μg · l−1 · (120 min)−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.

2000 ◽  
Vol 25 (2) ◽  
pp. 157-168 ◽  
Author(s):  
M Montero ◽  
L Yon ◽  
S Kikuyama ◽  
S Dufour ◽  
H Vaudry

Growth hormone-releasing hormone (GHRH) and pituitary adenylate cyclase-activating polypeptide (PACAP) belong to the same superfamily of regulatory neuropeptides and have both been characterized on the basis of their hypophysiotropic activities. This review describes the molecular evolution of the GHRH/PACAP gene family from urochordates to mammals and presents the hypothesis that the respective roles of GHRH and PACAP in the control of GH secretion are totally inverted in phylogenetically distant groups of vertebrates. In mammals, GHRH and PACAP originate from distinct precursors whereas, in all submammalian taxa investigated so far, including birds, amphibians and fish, a single precursor encompasses a GHRH-like peptide and PACAP. In mammals, GHRH-containing neurons are confined to the infundibular and dorsomedial nuclei of the hypothalamus while PACAP-producing neurons are widely distributed in hypothalamic and extrahypothalamic areas. In fish, both GHRH- and PACAP-immunoreactive neurons are restricted to the diencephalon and directly innervate the adenohypophysis. In mammals and birds, GHRH plays a predominant role in the control of GH secretion. In amphibians, both GHRH and PACAP are potent stimulators of GH release. In fish, PACAP strongly activates GH release whereas GHRH has little or no effect on GH secretion. The GHRH/PACAP family of peptides thus provides a unique model in which to investigate the structural and functional facets of evolution.


1981 ◽  
Vol 97 (4) ◽  
pp. 448-453 ◽  
Author(s):  
C. G. Scanes ◽  
S. Harvey ◽  
B. A. Morgan ◽  
M. Hayes

Abstract. Variations in plasma growth hormone (GH) concentrations following iv or sc administration of synthetic thyrotrophin-releasing hormone (TRH, Pyr-His-Pro-NH2) have been followed in immature and adult domestic fowl. TRH markedly stimulated GH secretion in newly hatched (1 and 2 day old) chicks and in 6-week-old cockerels but in adult male or female birds of two strains had very little effect, if any. Intravenous injection of 4 TRH analogues (Pyr-His-Mep-NH2, Pyr-Meh-Mep-NH2, Pyr-Meh-Mep-NH and Pyr-Meh-Pro-NH2) were also potent GH secretagogues in 6-week-old birds. The stimulatory effect of TRH or the TRH-analogues on GH secretion was not dose-related.


1996 ◽  
Vol 134 (1) ◽  
pp. 73-76 ◽  
Author(s):  
Giuseppe Fanciulli ◽  
Osvaldo Oliva ◽  
Paolo A Tomasi ◽  
Alessandra Pala ◽  
Alba Bertoncelli ◽  
...  

Fanciulli G, Oliva O, Tomasi PA. Pala A. Bertoncelli A, Dettori A, Delitala G. Effect of exogenous growth hormone administration on endogenous growth hormone secretion induced by a met-enkephalin analog. Eur J Endocrinol 1996:134:73–6. ISSN 0804–4643 Exogenous growth hormone (hGH) administration in humans attenuates the endogenous growth hormone (GH) response to some pharmacological stimuli: in particular, pretreatment with hGH completely blocks the serum GH response to growth hormone-releasing hormone. In order to evaluate the mechanism(s) whereby opioids induce GH secretion in man, we gave the following treatments to six healthy male volunteers: (a) IV saline: (b) a met-enkephalin analog G-DAMME 250 μg IV as a bolus at time ′: (c) hGH 2 IU as an IV bolus at time −180′; (d) G-DAMME as above, preceded by hGH as above. In our study. G-DAMME stimulated GH secretion both basally (peak 17.9 ± 6.0 ng/ml) and, to a lesser extent, after hGH pretreatment (6.0 ± 2.7 ng/ml). Since in our study G-DAMME was able to partially overcome the inhibitory effect of hGH administration, it is suggested that opioids act through an inhibition of somatostatin release and not through a GHRH-dependent pathway. However, an additional direct effect of hGH on pituitary somatotrophes cannot be excluded. Giuseppe Delitala, Chair of Endocrinology, Viale S. Pietro 12, University of Sassari, 07100 Sassari. Italy


1992 ◽  
Vol 126 (2) ◽  
pp. 113-116 ◽  
Author(s):  
SM Corsello ◽  
A Tofani ◽  
S Della Casa ◽  
R Sciuto ◽  
CA Rota ◽  
...  

Previous studies have shown that corticotropin-releasing hormone (CRH) is capable of inhibiting growth hormone (GH) secretion in response to GH-releasing hormone (GHRH). In an attempt to clarify the mechanism of the CRH action, we have studied the effect of enhanced cholinergic tone induced by pyridostigmine on the CRH inhibition of the GH response to GHRH in a group of six normal men and six normal women. All subjects presented a normal GH response to 50 μg iv GHRH administration (mean peak±sem plasma GH levels 20±2.9 μg/l in men and 28.9±2.9 μg/l in women) with a further significant increase after pyridostigmine pretreatment (60mg orally given 60 min before GHRH) in men (GH peaks 43.1±6.9 μg/l, p<0.005) but not in women (GH peaks 39.2±3.0 μg/l). In the same subjects, peripherally injected CRH (100 μg) significantly inhibited the GH response to GHRH (GH peaks 8.1±0.6 μg/l in men, p<0.005 and 9.9±0.7 μg/l in women, p<0.005). Pyridostigmine (60 mg) given orally at the same time of CRH administration (60 min before GHRH) reversed the CRH inhibition of GHRH-induced GH secretion (GH peaks 35.3±8.2 μg/l in men and 35±3.3 μg/l in women) with a response not significantly different to that seen in the pyridostigmine plus GHRH test. Our data confirm that pyridostigmine is capable of potentiating the GHRH-induced GH release in normal male but not female subjects. In addition, our studies show that the potentiating action of pyridostigmine on the GHRH-induced GH secretion prevails on the inhibiting effect of CRH when the two drugs are given together 1 h before GHRH injection. Both CRH and pyridostigmine could exert their action by modifying, in opposite ways, somatostatin release from the hypothalamus.


1974 ◽  
Vol 76 (3) ◽  
pp. 488-494 ◽  
Author(s):  
M. Peracchi ◽  
F. Cavagnini ◽  
A. E. Pontiroli ◽  
U. Raggi ◽  
A. Malinverni ◽  
...  

ABSTRACT The effects of intravenously administered aminophylline on growth hormone (GH) secretion have been studied in sixteen normal subjects and four acromegalic patients. Intravenous infusion of theophylline ethylenediamine 480 mg over a 30 min period did not alter the blood glucose and serum GH levels in six normal subjects but raised the plasma FFA by 88 %. By contrast, in four acromegalic patients theophylline administration resulted in a fall of the serum GH levels by 17.6–51.7 %, mean 36.5%. In ten normal subjects the infusion of the drug clearly blunted the GH response to insulin hypoglycaemia without modifying the decrease in blood glucose and plasma FFA induced by insulin: mean peak GH values decreased from 32.7 ± 3.39 to 21.4 ± 4.10 ng/ml (P < 0.025). These data seem to indicate that theophylline has an overall inhibiting effect on the hypothalamic-hypophyseal axis for GH secretion.


2002 ◽  
Vol 282 (4) ◽  
pp. E943-E951 ◽  
Author(s):  
Hiralal G. Maheshwari ◽  
Suzan S. Pezzoli ◽  
Asad Rahim ◽  
Stephen M. Shalet ◽  
Michael O. Thorner ◽  
...  

Growth hormone (GH) secretion is regulated by GH-releasing hormone (GHRH), somatostatin, and possibly ghrelin, but uncertainty remains about the relative contributions of these hypophysiotropic factors to GH pulsatility. Patients with genetic GHRH receptor (GHRH-R) deficiency present an opportunity to examine GH secretory dynamics in the selective absence of GHRH input. We studied circadian GH profiles in four young men homozygous for a null mutation in the GHRH-R gene by use of an ultrasensitive GH assay. Residual GH secretion was pulsatile, with normal pulse frequency, but severely reduced amplitude (<1% normal) and greater than normal process disorder (as assessed by approximate entropy). Nocturnal GH secretion, both basal and pulsatile, was enhanced compared with daytime. We conclude that rhythmic GH secretion persists in an amplitude-miniaturized version in the absence of a GHRH-R signal. The nocturnal enhancement of GH secretion is likely mediated by decreased somatostatin tone. Pulsatility of residual GH secretion may be caused by oscillations in somatostatin and/or ghrelin; it may also reflect intrinsic oscillations in somatotropes.


1972 ◽  
Vol 54 (3) ◽  
pp. 425-433 ◽  
Author(s):  
F. CAVAGNINI ◽  
M. PERACCHI ◽  
G. SCOTTI ◽  
U. RAGGI ◽  
A. E. PONTIROLI ◽  
...  

SUMMARY The effect of both oral and intravenous administration of l-DOPA on growth hormone (GH) secretion was studied in a group of normal volunteers: a significant rise of serum GH levels was observed in both cases. Growth hormone release in response to insulin hypoglycaemia and to arginine infusion was evaluated in a group of Parkinsonian patients before and after 25 days' treatment with l-DOPA plus a DOPA-decarboxylase inhibitor. In addition, GH response to the above stimuli was studied in a group of patients who had been under treatment for more than 6 months with l-DOPA alone. In untreated Parkinsonian patients, GH response to insulin hypoglycaemia was at the lower limit of normal range while arginine-induced GH release was significantly reduced. Treatment with l-DOPA did not increase GH responses. Some possible interpretations of the results are discussed. The findings support the possibility that dopamine plays a role in the physiological regulation of GH secretion, as in the case of luteinizing hormone, follicle-stimulating hormone and prolactin release.


1995 ◽  
Vol 146 (2) ◽  
pp. 227-232 ◽  
Author(s):  
A Giustina ◽  
A R Bussi ◽  
R Deghenghi ◽  
B Imbimbo ◽  
M Licini ◽  
...  

Abstract The aim of our study was to investigate the effect of hexarelin, a novel GH-releasing peptide-6 analog, and GH-releasing hormone (GHRH) (alone or in combination) on GH secretion in adult patients with increased somatostatin tone due to chronic glucocorticoid excess. We studied seven adult patients undergoing long-term (no less than 6 months) immunosuppressive glucocorticoid treatment for non-endocrine diseases (six females and one male, age range 42–68 years) and one subject (female, age 31 years) with endogenous hypercortisolism due to adrenal adenoma. Six normal subjects (four females and two males) matched for sex and age with the patients and not undergoing any therapy served as controls. All the subjects underwent the following three tests in random order: (1) human GHRH (1–29)NH2 (100 μg in 1 ml saline) injected as an i.v. bolus at 0 min, (2) hexarelin (100 μg in 1 ml saline) injected as an i.v. bolus at 0 min and (3) hexarelin (100 μg in 1 ml of saline) plus GHRH (100 μg in 1 ml saline) injected as an i.v. bolus at 0 min. After GHRH alone the patients with glucocorticoid excess showed a blunted GH response as compared with normal subjects (median delta GH: 0·9, range 0–5·6 μg/l vs 7·1, range 0·3–14·9 μg/l). No significant differences were observed in the steroid-treated group with respect to normal subjects after hexarelin alone (median delta GH: 15·5, range 1·9–45·2 μg/l vs 17·9, range 5·5–53·9 μg/l). The GH responses after the combined stimuli were significantly decreased in the patients with glucocorticoid excess as compared with normal subjects (median delta GH: 43·5, range 21–56·9 μg/l vs 73·7, range 19·6-116·8 μg/l). The two stimuli acted in a synergistic fashion in both groups of subjects. It may be hypothesized that hexarelin influences the GH inhibitory effect of glucocorticoids in humans, acting at the hypothalamic somatostatin level. Journal of Endocrinology (1995) 146, 227–232


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