Effect of cholinergic enhancement by pyridostigmine on growth hormone secretion in obese adults and children

Ghigo, Ezio; Mazza, Enrico; Corrias, Andrea; Imperiale, E.; Goffi, S.; Arvat, Emanuela; Bellone, J.; Sanctis, C. De; Müller, Eugenio E.; Camanni, F.

doi:10.1016/0026-0495(89)90099-1

Cited by 49 publications

(22 citation statements)

References 21 publications

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“…Because our study included only healthy otherwise unmedicated men, previously described differences in GH release due to gender or underlying illness were not variables in this investigation. Although pyridostigmine administration has been demonstrated to potentiate spontaneous diurnal GH secretion in short children (43) and to counteract the blunted GH response to GHRH in both obese children and adults (6), regression analysis of our data suggested that this cholinergic agonist is unable to reverse completely the suppression of GH release that is associated with increasing adiposity. Indeed, BMI was a strongly negative determinant of both pyridostigminestimulated GH secretory burst mass and daily GH production (Fig.…”

Section: Placebo Pyridostigminementioning

confidence: 41%

“…Within the cholinergic system, muscarinic receptors have been demonstrated to modulate the GH axis; antagonists such as atropine inhibit GHRH-induced GH release, while inhibitors of acetylcholinesterase (indirect cholinergic agonists) such as pyridostigmine generally serve to facilitate GH secretion. Pyridostigmine administration, for example, potentiates spontaneous diurnal GH secretion in short children (4) and counteracts the blunted GH response to GHRH in obese children and adults (5,6). Additionally, in rats, treatment with the direct cholinergic agonist, pilocarpine, can partially reverse some of the agerelated decline in the GH response to a GHRH bolus (7).…”

Section: Introductionmentioning

confidence: 99%

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Pyridostigmine treatment selectively amplifies the mass of GH secreted per burst without altering GH burst frequency, half-life, basal GH secretion or the orderliness of GH release

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Iranmanesh²,

et al. 1997

European Journal of Endocrinology

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Growth hormone (GH) release from the anterior pituitary gland is predominantly regulated by the two antagonistic hypothalamic peptides, growth hormone-releasing hormone (GHRH) and somatostatin. Appraising endogenous GHRH action is thus made difficult by the confounding effects of (variable) hypothalamic somatostatin inhibitory tone. Accordingly, to evaluate endogenous GHRH actions, we used a clinical model of presumptively acute endogenous somatostatin withdrawal with concomitant GHRH release. To this end, we administered in randomized order placebo or the indirect cholinergic agonist, pyridostigmine, for 48 h to 13 healthy men of varying ages (29-77 years) and body mass indices (21-47 kg/m 2 ). We sampled blood at 10-min intervals for 48 h during both placebo and pyridostigmine (60 mg orally every 6 h) administration, and used an ultrasensitive GH chemiluminescence assay (sensitivity 0.002-0.005 mg/l) to capture GH pulse profiles. Multiparameter deconvolution analysis was applied to quantitate the number, amplitude, mass, and duration of significant underlying GH secretory bursts, and simultaneously estimate the GH half-life and concurrent basal GH secretion. Approximate entropy was utilized as a novel regularity statistic to quantify the relative orderliness of the hormone release process. All measures of GH secretion/half-life and orderliness were statistically invariant across the two consecutive 24-h placebo sessions. In contrast, pyridostigmine treatment significantly increased the mean serum GH concentration from 0.23 Ϯ 0.054 mg/l during placebo to 0.45 Ϯ 0.072 mg/l during the first day of treatment (P < 0.01). There was also a significant rise in the calculated 24-h pulsatile GH production rate from 8.9 Ϯ 1.7 mg/l/day on placebo to 27 Ϯ 5.6 mg/l/day during active drug treatment (P < 0.01). Pyridostigmine significantly and selectively amplified GH secretory burst mass to 1.5 Ϯ 0.35 mg/l compared with 0.74 Ϯ 0.19 mg/l on placebo (P < 0.01). This was attributable to stimulation of GH secretory burst amplitude (maximal rate of GH secretion attained within the release episode) with no prolongation of estimated burst duration. Basal GH secretion and approximate entropy were not altered by pyridostigmine. However, age was strongly related to more disorderly GH release during both days of pyridostigmine treatment (r = +0.79, P = 0.0013). During the second 24-h of continued pyridostigmine treatment, most GH secretory parameters decreased by 15-50%, but in several instances remained significantly elevated above placebo. Body mass index, but not age, was a significantly negative correlate of the pyridostigminestimulated increase in GH secretion (r = ¹0.65, P = 0.017).In summary, assuming that somatostatin is withdrawn and (rebound) GHRH release is stimulated via pyridostigmine administration, we infer that relatively unopposed GHRH action principally controls GH secretory burst mass and amplitude, rather than apparent GH secretory pulse duration, the basal GH secretion rate, or the serial regularity/orderli...

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Section: Placebo Pyridostigminementioning

confidence: 41%

Section: Introductionmentioning

confidence: 99%

Pyridostigmine treatment selectively amplifies the mass of GH secreted per burst without altering GH burst frequency, half-life, basal GH secretion or the orderliness of GH release

Friend

Iranmanesh²,

et al. 1997

European Journal of Endocrinology

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“…8,13 More recently, it has been clearly demonstrated that hypothalamic SS is not increased in obese rats which show reduced pituitary GH content as well as low hypothalamic GHRH content. 21 In humans, we have found that 8 day GHRH pretreatment enhanced the low GH response to GHRH in elderly subjects but did not affect that in obese patients.…”

mentioning

confidence: 99%

The GH/IGF-I axis in obesity: influence of neuroendocrine and metabolic factors

et al. 2000

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In this review we propose an integrated neuro-endocrine-metabolic point of view on the alterations (adaptations?) of GHaIGF-1 axis in obesity, summarizing the evidence from the literature, particularly focusing the data on humans and adding where possible results from our studies in this ®eld. It is well-known that GH secretion is deeply impaired in overweight patients: we reviewed the multiple mechanisms underlying this issue, considering either central (CNS-related, such as impairment of GHRH tone or increased somatostatin release) or peripheral (ie metabolic: insulin, free fatty acids, glucose) factors. A central point of the debate about GH insuf®ciency in obesity is if it represents a simple adaptive phenomenon or re¯ects a true impairment of the axis activity. Evaluation of IGF-I levels and generation in obesity was the mean used to address this question: a bulk of evidence on IGF-I balance in human obesity has been provided, but the matter is still uncertain and unsolved.

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“…The dual mechanism postulated for pyridostigmine would account more convincingly for the inability of cholinergic agonists to reverse completely the defective GH release associated with increased adiposity (24,25) than would a mechanism relying exclusively on inhibition of hypothalamic somatostatin. Complete reversion of the GH hyposecretion is obtained instead, in obesity, by the combined administration of GHRH and GHs (26), which provides an appropriate GHRH and anti-SS stimulation.…”

Section: Cholinergic Mediation: a 'Pure' Antisomatostatin Mechanism?mentioning

confidence: 99%

Cholinergic function and neural control of GH secretion. A critical re-appraisal

Müller

1997

European Journal of Endocrinology

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Effect of cholinergic enhancement by pyridostigmine on growth hormone secretion in obese adults and children

Cited by 49 publications

References 21 publications

Pyridostigmine treatment selectively amplifies the mass of GH secreted per burst without altering GH burst frequency, half-life, basal GH secretion or the orderliness of GH release

Pyridostigmine treatment selectively amplifies the mass of GH secreted per burst without altering GH burst frequency, half-life, basal GH secretion or the orderliness of GH release

The GH/IGF-I axis in obesity: influence of neuroendocrine and metabolic factors

Cholinergic function and neural control of GH secretion. A critical re-appraisal

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