Dopaminergic and Cholinergic Influences on the Growth Hormone Response to Growth Hormone-Releasing Hormone in Man

Delitala, G.; Palermo, Mario; Ross, R. J. M.; Coy, David C.; Besser, Michael; Grossman, Ashley

doi:10.1159/000124732

Cited by 41 publications

(21 citation statements)

References 17 publications

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“…The time elapsed from when bromocriptine was given in these studies [6,8] and when its GH-secreting effects were observed are both compatible with that observation [35] and our hypothesis on adrenergic-mediated central effects of DA on SS secretion. It would be interest ing to test GH responses to GHRH given at shorter intervals following bromocriptine administration.…”

Section: Discussionsupporting

confidence: 89%

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Role of Central Dopaminergic Pathways in the Neural Control of Growth Hormone Secretion in Normal Men: Studies with Metoclopramide

et al. 1991

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The aim of this study was to gain further insight into the role that central dopaminergic pathways play in GH neuroregulation in man. Our experimental hypothesis was based on the possibility that most of the controversies on DA role could be due to the fact that the hypothalamic somatotroph rhythm (HSR) was not taken into account when interpreting the GH responses after pharmacological manipulations on dopaminergic pathways. In 10 normal subjects we monitored the effect of central dopaminergic blockade, achieved with metoclopramide (MCP; 10 mg, i.v. bolus), on the pattern of spontaneous GH secretion and the GH responses to a GHRH challenge (GRF_1–29, 1 µg/kg, i.v. bolus) administered together with MCP or 60 min after this drug was given. The study of HSR was made according to our previous postulate. Our results indicate that MCP administration, either prior to or together with the GHRH bolus, significantly increased GHRH-induced GH release during a refractory HSR phase; but not when the GHRH challenge took place during a spontaneous secretory phase. The strong relationship between pre-GHRH plasma GH values and GHRH-elicited GH peaks was lost when MCP was given. These data indicate that MCP was able to disrupt the intrinsic HSR by inhibiting the hypothalamic release of somatostatin (SS). While a main conclusion would be that central DA is a secretagogue for SS secretion, our results also suggest that this role could be dependent on its effects on the adrenergic inputs to SS neurons.

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Section: Discussionsupporting

confidence: 89%

“…This hypothesis is not inconsistent with the demonstration that DA and bromocriptine augmented the GHRH-induced GH response in normal man [6,8], In these studies, bromocrip tine administration induced a spontaneous GH secretion begin ning 90 min later. GHRH challenge at these times elicited a significant GH release in both experiments.…”

Section: Discussionmentioning

confidence: 48%

Role of Central Dopaminergic Pathways in the Neural Control of Growth Hormone Secretion in Normal Men: Studies with Metoclopramide

et al. 1991

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“…In the last few years a large body of both direct and circum stantial evidence has established that acetylcholine regulates GH secretion by tonically inhibiting somatostatin release by the hypothalamus [9,10,20,21 ]. In agreement with this hypothesis, the inhibitory feedback exerted by GH and GHRH on GH se cretion can be overcome by cholinergic activation by pyridostig mine and the resulting blockade of somatostatin release [ 10,22,23).…”

Section: Discussionmentioning

confidence: 87%

Activation of Cholinergic Neurotransmission by Pyridostigmine Reverses the Inhibitory Effect of Hyperglycemia on Growth Hormone (GH) Releasing Hormone-Induced GH Secretion in Man: Does Acute Hyperglycemia Act through Hypothalamic Release of Somatostatin?

Peñalva¹,

Burguera²,

Casabiell³

et al. 1989

Neuroendocrinology

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Acute hyperglycemia blocks growth hormone (GH) secretion in response to provocative stimuli including growth hormone releasing hormone (GHRH) administration. However, the precise mechanism of glucose action is unknown. To determine if enhanced somatostatinergic stimulation accounts for the decreased GH secretion, we studied the effect of enhanced cholinergic tone by pyridostigmine on the hyperglycemia blockade of GH release in 7 normal subjects. Pyridostigmine, an acetylcholin-esterase inhibitor, has been postulated as an inhibitor of somatostatin release. Each subject underwent 4 tests with GHRH injection (100 µg i.v. at 0 min). In the first (control) test, placebo was administered before GHRH. In the second test, 100 g of glucose was administered p.o. 45 min before GHRH. In the third test, pyridostigmine, 120 mg p.o., was administered 60 min before GHRH, and in the fourth test, pyridostigmine, glucose and GHRH were administered at -60, -45 and 0 min, respectively. GHRH-induced GH secretion of 25.8 ± 4.5 ng/ml was significantly reduced by previous glucose administration (12.1 ± 4.5 ng/ml) and significantly potentiated by previous pyridostigmine pretreatment (56.5 ± 16.8 ng/ml). In the fourth test (pyridostigmine plus glucose plus GHRH) the GH peak of 42.4 ± 9.2 ng/ml was significantly higher than after GHRH alone and not different to the pyridostigmine-GHRH test. In conclusion, central cholinergic activation by pyridostigmine reversed the hyperglycemic blockade of GHRH-induced GH secretion. In addition, hyperglycemia was unable to reduce the potentiating effect of pyridostigmine on GH secretion elicited by GHRH. Based on the reported actions of pyridostigmine, acute hyperglycemia might act over GH release by inducing hypothalamic somatostatin release.

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“…Similarly, the GH responsive ness to GHRH bolus injection is clearly enhanced by bromo criptine pretreatment [7, 31 ]. The conclusion from these studies was that, in the presence of a pharmacological dose of GHRH, enhanced GH release during dopaminergic stimulation oc curred by a reduction in hypothalamic somatostatin release.…”

Section: Discussionmentioning

confidence: 99%

Pyridostigmine Potentiates L-Dopa- but not Arginine- and Galanin-Induced Growth Hormone Secretion in Children

et al. 1990

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The coadministration of growth hormone (GH) secretagogues can provide insight into the neuroregulation of GH secretion. The GH response to L-dopa (125, 250 and 500 mg orally for body weights < 15 kg, between 15 and 30 kg and > 30 kg, respectively), arginine (Arg; 0.5 g/kg infused intravenously over 30 min) and galanin (GAL; 15 µg/kg infused intravenously over 60 min) when administered alone or combined with Pyridostigmine (PD; 60 mg orally), a cholinergic agonist that likely acts via inhibition of endogenous somatostatin secretion, was studied in children with familial short stature. The GH-releasing effect of PD was also evaluated. In 8 children, PD and L-dopa when administered alone induced an equivalent GH rise (area under the response curve, mean ± SEM: 241.4 ± 31.1 vs. 202.9 ± 38.6 µg/l/h) while their coadministration had an additive effect (435.4 ± 41.4 µg/l/h; p < 0.02 vs. PD and L-dopa alone). On the contrary, in other 8 children, PD and Arg induced similar GH increases either when administered alone (394.2 ± 68.5 vs. 405.8 ± 103.9 µg/l/h) or in combination (535.8 ± 97.3 µg/l/h). GH increases almost superimposable were also observed when PD and GAL were administered alone (405.2 ± 72.3 vs. 412.6 ± 94.1 µg/l/h) or in combination (537.9 ± 139.0 µg/l/h) in other 7 children. These data show that the enhancement of the cholinergic activity by PD increases the L-dopa-induced GH release but fails to modify both Arg- and GAL-induced GH release in short children. They may be taken to indicate that a common mechanism, i.e. suppression of endogenous somatostatin secretion, underlies the GH-releasing effect of PD, Arg and GAL, while an extra-somatostatinergic mechanism mediates the effect of L-dopa.

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Dopaminergic and Cholinergic Influences on the Growth Hormone Response to Growth Hormone-Releasing Hormone in Man

Cited by 41 publications

References 17 publications

Role of Central Dopaminergic Pathways in the Neural Control of Growth Hormone Secretion in Normal Men: Studies with Metoclopramide

Role of Central Dopaminergic Pathways in the Neural Control of Growth Hormone Secretion in Normal Men: Studies with Metoclopramide

Activation of Cholinergic Neurotransmission by Pyridostigmine Reverses the Inhibitory Effect of Hyperglycemia on Growth Hormone (GH) Releasing Hormone-Induced GH Secretion in Man: Does Acute Hyperglycemia Act through Hypothalamic Release of Somatostatin?

Pyridostigmine Potentiates L-Dopa- but not Arginine- and Galanin-Induced Growth Hormone Secretion in Children

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