Atropine Blockade of Growth Hormone (GH)-Releasing Hormone-Induced GH Secretion in Man Is not Exerted at Pituitary Level*

Casanueva, Felipe F.; Villanueva, Luis; Diéguez, Carlos; Cabranes, José A.; Diaz, Y.; Szőke, Balázs; Scanlon, M. F.; Schally, Andrew V.; Fernández-Cruz, A

doi:10.1210/jcem-62-1-186

Cited by 88 publications

(42 citation statements)

References 25 publications

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“…Pirenzepine is a mus carinic cholinergic antagonist that blocks the GH response to a variety of stimuli, but not insulin-induced hypoglycaemia [9][10][11]. Our finding of partial blockade of the GH response to GHRH by pirenzepine supports an earlier re port [22], as well as a more recent study by Casanueva et al [5] using atropine. As pirenzepine only poorly penetrates the blood-brain barrier [15], ant there is no evidence for a direct cholinergic modulation of pituitary GH release [3.…”

Section: Discussionsupporting

confidence: 89%

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

et al. 1987

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It is well established that compounds that modify dopaminergic and cholinergic activity in man may induce changes in circulating growth hormone (GH). We have, therefore, investigated the effect of a dopamine agonist, bromocriptine, and a dopamine antagonist, domperidone, as well as a muscarinic cholinergic antagonist, pirenzepine, on the GH response to an analogue of GH-releasing hormone (GHRH) in normal male subjects. GHRH(1–29)NH₂ induced a rise in serum GH that was augmented by bromocriptine, antagonized by pirenzepine, but was unaltered by domperidone. As this dose of GHRH(l-29) NH₂ has been shown to be maximally stimulatory to GH release, it is suggested that there are dopamine stimulatory and cholinergic inhibitory receptors to GH release independent of GHRH in man.

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Section: Discussionsupporting

confidence: 89%

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

et al. 1987

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“…Administration of the cholinergic muscarinic blocker atropine, which acts by increasing hypothalamic somatostatinergic tone and inhibiting GHRH release [43, 45], completely blunted the GH response to SUM. Theoretically, this could be due to either the possibility that SUM does not act via somatostatin or, alternatively, that the activation of 5-HT 1D receptors is unable to counteract the stimulatory effect of atropine on somatostatin.…”

Section: Discussionmentioning

confidence: 99%

Influence of Different Serotonin Receptor Subtypes On Growth Hormone Secretion

Valverde

Peñalva²,

Diéguez

2000

Neuroendocrinology

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The role of serotonin (5-HT) in the regulation of growth hormone (GH) secretion remains unclear due to the existence of many different receptors that mediate the 5-HT actions, and the lack of suitable specific agonist and antagonist drugs. In the present work we have taken advantage of the recent development of new selective 5-HT drugs in order to clarify the role played by different 5-HT receptor types and subtypes on GH secretion. The experiments were carried out on beagle dogs. GH-releasing hormone (GHRH) increased basal canine GH (cGH) levels from 0.8 ± 0.2 to 8.8 ± 1.7 µg/l at 15 min. Administration of 5-HT_1D receptor agonist sumatriptan (SUM) induced a cGH peak at 30 min of 12.9 ± 2.7 µg/l. The combined administration of GHRH plus SUM strikingly potentiated cGH release with a peak of 36.9 ± 6 µg/l at 30 min (p < 0.05). Pretreatment with the muscarinic receptor antagonist atropine completely abolished the cGH response to SUM, while the cholinergic agonist pyridostigmine (PYR) did not modify this response (15.3 ± 5 µg/l PYR plus SUM vs. SUM alone 12.9 ± 2.7 µg/l). On the other hand, administration of drugs with activity at 5-HT_2A/C receptors showed a stimulatory role for the 5-HT_2C receptor subtype, since LY-53857 (antagonist 5-HT_2A/C) and DOI agonist (5-HT_2A/C) both modified the GH response stimulated by GHRH (AUC 88.5 ± 30.4 and 400 ± 64.6 vs. 267.3 ± 52.6 respectively), while ketanserin (antagonist 5-HT_2A) did not modify this response. The 5-HT₃ antagonist ICS-205–930 failed to modify either basal or GHRH induced GH responses. In conclusion, our data show that 5-HT_1D receptors play a stimulatory role on GH secretion in the dog, possibly by acting through a decrease in hypothalamic somatostatin release. Similarly, the 5-HT_2C receptor subtypes also appear to play a stimulatory role. However, 5-HT_2A and 5-HT₃ receptors do not appear to be involved in the control of basal and GHRH-induced GH secretion.

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“…This suggests that the action of pyridostigmine is mediated not by the stimulation of GHRH release but either by the inhibition of somatostatin secretion or the stimulation of some other GH-releasing factor. A direct effect at the level of the pituitary seems unlikely as anticholidergic and cholinergic drugs had no effect on the GH response to GHRH in anterior pituitary cell cultures (3,5 in animals suggest that the effect of cholinergic manipulation on GH secretion is mediated through alteration of hypothalamic somatostatin secretion. Acetylcholine inhibits somatostatin release from the rat hypothalamus (4), and the effects of cholinergic manipulation on GH secretion in rats was abolished by hypothalamic somatostatin depletion (5).…”

Section: Discussionmentioning

confidence: 99%

“…They act rehpectively to inhibit and stimulate GH release from the pituitary. The release of the hypothalamic peptides is in turn influenced by various neurotransmitters, for example cholinergic agonists increase and antagonists decrease GH release (2,3). Data in animals suggest that the effects of altered cholinergic tone are mcdiated through alterations in hypothalamic somatostatin secretion (4,5).…”

mentioning

confidence: 99%

Pyridostigmine, an Acetylcholinesterase Inhibitor, Stimulates Growth Hormone Release, but has no Effect on Basal Thyrotrophin or Adrenocorticotrophin Levels, or the Thyrotrophin Response to Thyrotrophin‐Releasing Hormone

Freeman

Touzel

Grossman

et al. 1990

J Neuroendocrinology

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Pyridostigmine, an acetylcholinesterase inhibitor, stimulates growth hormone (GH) release and is thought to act by inhibiting hypothalamic somatostatin release. There are few data concerning the effect of pyridostigmine on other pituitary hormones apart from GH. We have studied the effect of pyridostigmine on basal GH, thyrotrophin (TSH), prolactin, adrenocorticotrophin and cortisol release, and thyrotrophin-releasing hormone (TRH)-stimulated TSH and prolactin release, in two studies involving nine healthy male subjects. Pyridostigmine stimulated GH release in all subjects but had no effect on adrenocortocotrophin or cortisol levels, or basal or TRH-stimulated TSH and prolactin levels.There are some data to suggest that somatostatin inhibits TRH-stimulated TSH release. Our findings, however, suggest that either endogenous somatostatin tone has little effect on the TSH response to TRH compared to its effects on GH or pyridostigmine acts through a mechanism other than altering somatostatin tone. Pyridostigmine did not alter adrenocorticotrophin or cortisol levels in the presence of a clear action on GH release, providing further evidence that the previously reported effects of cholinergic drugs on cortisol release are stress-relatedThe pulsatile release of growth hormone (GH) results from a d! namic equilibrium between the two hypothalamic hormones, Somatostatin and GH-releasing hormone (GHRH) (1). They act rehpectively to inhibit and stimulate GH release from the pituitary. The release of the hypothalamic peptides is in turn influenced by various neurotransmitters, for example cholinergic agonists increase and antagonists decrease GH release (2, 3). Data in animals suggest that the effects of altered cholinergic tone are mcdiated through alterations in hypothalamic somatostatin secretion (4, 5). Pyridostigmine, an acetylcholinesterase inhibitor, augments cholinergic tone, and increases both basal and GHRHstimulated GH release (6, 7). To date, there are few data concerning the effect of altered cholinergic tone on the release of other pituitary hormones. Exogenous somatostatin inhibits the thyrotrophin (TSH) response to thyrotrophin-releasing hormone (TKH) (8,9), and therefore it might be expected that alterations in cholinergic tone could influence TSH release. In vitro, acetylcholine causes release of corticotrophin-releasing factor (10, 11) but its effects in vivo remain unclear (12). We have therefore studied the effect of pyridostigmine on basal GH, TSH, prolactin and adrenocorticotrophin (ACTH) release, and the TSH, GH and prolactin responses to TRH. Results Study IIn all six subjects GH levels rose 60 to 120 min after pyridostigmine and were higher than after placebo alone. After 60 min the mean peak serum GH level after placebo was 3.8 (range, < 1.0 to 9.0) mU/1 compared to 23.0 (5.5 to 52.6) mU/1 after pyridostigmine (P=O.O36). There was no consistent change in either ACTH or cortisol levels after pyridostigmine as compared to placebo (Fig. I), but in one subject ACTH levels rose from 13 ng/l at t...

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Atropine Blockade of Growth Hormone (GH)-Releasing Hormone-Induced GH Secretion in Man Is not Exerted at Pituitary Level*

Cited by 88 publications

References 25 publications

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

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

Influence of Different Serotonin Receptor Subtypes On Growth Hormone Secretion

Pyridostigmine, an Acetylcholinesterase Inhibitor, Stimulates Growth Hormone Release, but has no Effect on Basal Thyrotrophin or Adrenocorticotrophin Levels, or the Thyrotrophin Response to Thyrotrophin‐Releasing Hormone

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