Responsiveness of pituitary hGH to GRH1-44 in juveniles with obesity

Pertzelan, A; Keret, R; Bauman, B; Josefsberg, Z; Ben-Zeev, Z.; Szőke, Balázs; Comaru-Schally, A. M.; Laron, Zvi

doi:10.1530/acta.0.1110151

Cited by 13 publications

(13 citation statements)

References 5 publications

(10 reference statements)

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“…The blunted GH response to a single bolus injec¬ tion of GHRH, as shown in this study, confirms previous reports (Pertzelan et al 1986;Pintor et al 1986;Loche et al 1987), and, as previously ob¬ served (Loche et al 1987;Rosskamp et al 1987), this blunted response was associated with high im¬ munoreactive Sm-C levels. A tendency to high Sm-C levels in obese prepubertal children associ¬ ated with reduced 24-hour GH secretion has also recently been reported by Minuto et al (1988).…”

Section: Discussionsupporting

confidence: 92%

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Pyridostigmine counteracts the blunted growth hormone response to growth hormone-releasing hormone of obese children

Loche

Pintor

Cappa³

et al. 1989

Acta Endocrinologica

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We have evaluated the effect of acute administration of pyridostigmine bromide, a cholinesterase inhibitor, on the GHRH-induced GH rise in 11 obese children and in 8 age-matched controls. The GH response to GHRH (hpGRF 1\p=n-\40, 1 \g=m\g/kg iv), evaluated both as maximum GH peak and as integrated area under the curve, was significantly lower in the obese children than in the controls. Pretreatment with pyridostigmine bromide (60 mg orally 60 min before the GHRH injection) significantly increased both baseline GH levels and the GH response to GHRH in all the obese subjects, so that their mean baseline GH, peak GH levels and integrated area under the curve after pyridostigmine bromide plus GHRH were similar to those of the control children after GHRH. Also in control children pyridostigmine bromide increased (though not significantly) baseline GH levels, and caused a significant augmentation of the GH response to GHRH. Mean peak GH levels and mean integrated area under the curve after pyridostigmine bromide plus GHRH were significantly higher in the controls than in the obese children given the same treatment. Mean baseline Sm-C levels were significantly higher in the obese than in control children. These data show that enhancement of cholinergic neurotransmission, likely in the hypothalamus, counteracts the blunted GH response to GHRH present in the obese children, and that in simple obesity the potential of the pituitary to make a secretory response to a direct GH secretagogue is preserved.

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Section: Discussionsupporting

confidence: 92%

“…Reduced GH responses to a wide variety of stimuii (see Glass et al 1981 for review), inciuding GHRH (Williams et al 1984;Kopelman et al 1985;Pertzelan et al 1986;Pintor et al 1986) is a characteristic feature of obese subjects. We (Loche et af.…”

mentioning

confidence: 99%

Pyridostigmine counteracts the blunted growth hormone response to growth hormone-releasing hormone of obese children

Loche

Pintor

Cappa³

et al. 1989

Acta Endocrinologica

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“…Both spontaneous as well as stimulated GH secretion is reduced in obese children [31,32] and augmented dur ing starvation [33], while inverse changes are seen in serum IGF-I [34,35], At the cellular level, GH acutely down-regulates GH receptors in liver [36], whereas chronic administration augments hepatic GH binding [37] . The influence of nutrition on serum GHBP is likely to involve other hormonal mediators.…”

Section: Discussionmentioning

confidence: 99%

Binding Protein for Human Growth Hormone: Effects of Age and Weight

Holl¹,

Snehotta²,

Siegler³

et al. 1991

Horm Res

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In human serum, a specific binding protein with high affinity for human growth hormone (GHBP) is found which is identical to the extracellular portion of the hepatic GH receptor. GHBP is assessed by incubating serum samples with [¹²⁵I]-GH, followed by separation of bound and free radioactivity using gel chromatography. In newborns and children younger than 2 months, GHBP was practically absent and no ‘big-big’ GH could be found. GHBP values increased rapidly during the first 2 years of life, followed by a slower increase during childhood and puberty. No difference was found between male and female subjects. Apart from age, standardized weight (SDS = z score) had a major positive effect on GHBP concentration. Interestingly, SDS height correlated negatively with GHBP when weight and age were controlled for. These data may relate to two clinical findings: (1) the developmental switch between GH-independent intrauterine and GH-dependent postnatal growth mechanisms, and (2) the accelerated growth velocity encountered in adipose children.

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“…It has also been shown that these patients have decreased GH responses to GH-releasing hormone (9)(10)(11)(12)(13)(14). This could be due to reduced pituitary sensitivity to GHRH, excess of hypothalamic somatostatin, or a chronic state of GHRH deficiency.…”

mentioning

confidence: 99%

Pyridostigmine enhances, but does not normalise, the GH response to GH-releasing hormone in obese subjects

Castro

Vieira²,

Chacra³

et al. 1990

Acta Endocrinologica

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Obese patients are characterised by several neuroendocrine abnormalities, including characteristically a decrease in growth hormone responsiveness to GH-releasing hormone. In normal subjects, the GH response to GHRH is enhanced by the acetylcholinesterase inhibitor, pyridostigmine. We have studied the effect of this drug on GH secretion in gross obesity. Twelve obese patients were studied (mean weight 156% of ideal) and compared with a group of 8 normal volunteers. Each subject was initially studied on two occasions, in random order, with GHRH (1-29) NH2 100 \g=m\g iv alone and following pretreatment with pyridostigmine 120 mg orally one hour prior to GHRH. In obese patients, the GH response to GHRH was significantly blunted when compared to controls (GH peak: 20 \ m=+-\4 vs 44 \m=+-\16 \g=m\g/l ; mean \ m=+-\ sem). After pyridostigmine, the response to GHRH was enhanced in the obese subjects, but remained significantly reduced compared to non-obese subjects treated with GHRH and pyridostigmine (GH peak: 30 \ m=+-\5 vs 77 \ m=+-\20 \g=m\g/l ,respectively). In 6 subjects, higher doses of GHRH or pyridostigmine did not further increase GH responsiveness in obese patients. Our results suggest that obese patients have a disturbed cholinergic control of GH release, probably resulting from increased somatostatinergic tone. This disturbed regulation may be responsible, at least in part, for the blunted GH responses to provocative stimuli.Obese patients have blunted growth hormone re¬ sponses to a wide variety of stimuli (1-8). It has also been shown that these patients have decreased GH responses to GH-releasing hormone (9-14). This could be due to reduced pituitary sensitivity to GHRH, excess of hypothalamic somatostatin, or a chronic state of GHRH deficiency. Several lines of evidence point to a role for somatostatin in the de¬ creased GH release found in obesity. Obese pa¬ tients have blunted thyroid stimulating hormone response to TSH-releasing hormone (15), which might also reflect an increase in somatostatinergic tone. Furthermore, genetically-obese rats have in¬ creased hypothalamic somatostatin content (16) and increased hypothalamic somatostatin release in vitro (17). However, there is little direct evidence in the human.Pyridostigmine is a drug which activates cholinergic receptors by decreasing the activity of acetylcholinesterase, and enhances GH responsiveness to ; this is considered to occur via the inhibition of hypothalamic somatostatin (22). Recent studies have suggested that pyridostigmine may increase the GH response to GHRH in obesity, but only single doses of the drug were used, which did not take into account the increased body weight of the obese group compared to the controls (23,24).In order to investigate whether hypothalamic so¬ matostatin activity is increased in obesity, we have therefore studied the effect of several doses of py¬ ridostigmine on the GH response to GHRH in obese patients.

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Responsiveness of pituitary hGH to GRH1-44 in juveniles with obesity

Cited by 13 publications

References 5 publications

Pyridostigmine counteracts the blunted growth hormone response to growth hormone-releasing hormone of obese children

Pyridostigmine counteracts the blunted growth hormone response to growth hormone-releasing hormone of obese children

Binding Protein for Human Growth Hormone: Effects of Age and Weight

Pyridostigmine enhances, but does not normalise, the GH response to GH-releasing hormone in obese subjects

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