Very-low-calorie diet-induced weight reduction reverses impaired growth hormone secretion response to growth hormone-releasing hormone, arginine, and l-dopa in obesity

Tanaka, Katsuaki; Inoue, Shuji; Numata, Kazushi; Okazaki, Hiroshi; Nakamura, Saburo; Takamura, Yutaro

doi:10.1016/0026-0495(90)90296-o

Cited by 60 publications

(31 citation statements)

References 29 publications

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“…25 Finally, the postprandial insulin increase could exert such an effect through its own receptors or IGF-I receptors. 26 The fasting hyposecretory state is reversed by weight loss obtained either by dieting 4 or surgical procedures. 3 Williams et al 3 showed that weight loss, obtained by surgical by-pass, induces a normalisation of the GH response to GHRH, when the subjects were tested in the fasting state.…”

Section: Discussionmentioning

confidence: 99%

Evaluation of pre- and postprandial growth hormone (GH)-releasing hormone-induced GH response in subjects with persistent body weight normalisation after biliopancreatic diversion

Marinis¹,

Mancini²,

Valle

et al. 1998

Int J Obes

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BACKGROUND: Obesity is characterised by growth hormone (GH) abnormalities, including a blunted response to stimulation and a`paradoxical' increase after meals. The blunted GH release is reversed by a surgical intestinal bypass procedure. However, this does not mean that normal GH dynamics have been restored. The present study assessed whether post-surgical weight reduction in obese patients normalised the modulation of GH release produced by metabolic fuels. SUBJECTS: Ten obese female subjects, aged 23 ± 54 y, were studied before and after biliopancreatic diversion (BPD). All patients, after surgery, had experienced a signi®cant reduction in body weight (mean body mass index (BMI) 25.78 AE 1.01 kgam 2 vs 44.68 AE 1.73 kgam 2 ). Two groups were also studied as controls: Ten normal body weight female subjects and ten patients suffering from anorexia nervosa (AN, mean BMI 17.46 AE 1.12 kgam 2 ). MEASUREMENTS: We have studied the GH response to a GH releasing hormone (GHRH) bolus (1 m mgakg iv, at 13.00 h) before and after a standard meal. RESULTS: In post-BPD subjects, the GH response to GHRH in the fasting state, was clearly augmented in comparison with the pre-BPD values (peak values 18.06 AE 4.56 vs 3.24 AE 0.68 m mgaL). In post-BPD subjects the postprandial GH response was further augmented in comparison with the fasting test (peak 30.12 AE 4.99 m mgaL, P`0.05). This pattern was similar to that observed in anorexic patients. CONCLUSION: The surgical procedure restores a normal GH response to GHRH in the fasting state, but thè paradoxical' GH response after meals remains present, suggesting a persistent GH derangement in such patients, which is not related to body weight per se. The surgical procedure makes obese patients similar to anorexics, in the relationships between metabolic fuels and GH secretion. The persistence of the GH postprandial response to GHRH in post-BPD subjects suggests a role for metabolic fuels in the regulation of somatostatin (SRIF) secretion.

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Section: Discussionmentioning

confidence: 99%

Evaluation of pre- and postprandial growth hormone (GH)-releasing hormone-induced GH response in subjects with persistent body weight normalisation after biliopancreatic diversion

Marinis¹,

Mancini²,

Valle

et al. 1998

Int J Obes

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“…12,13,17,18,21,23,40 Con®rm-ing the metabolic pathogenesis of GH de®ciency in obesity there is the well known evidence that spontaneous and stimulated GH secretion are restored by weight loss 2,6 and that a clear inverse relationship exists between GH secretion and body mass. 2 From a diagnostic point of view, it has to be considered that the diagnosis of GH de®ciency in adulthood is still a matter of debate though there is clear evidence for usefulness of rhGH replacement.…”

Section: Discussionmentioning

confidence: 99%

“…In fact, there is evidence showing that GH secretion in obesity is restored by weight loss. 2,6 Moreover, clinical data and IGF-I levels are able to distinguish between obesity and hypopituitarism. 45 In all, our present data show that the pituitary GH releasable pool in obesity is impaired to an extent frequently overlapping with that in organic GH de®-ciency.…”

Section: Discussionmentioning

confidence: 99%

“…1±5 Interestingly, GH insuf®ciency in obesity is acquired and normal somatotrope function is restored by weight loss. 2,6,7 The pathogenesis of GH insuf®ciency in obesity is still unclear. Hypothalamic somatostatinergic hyperactivity and/or GHRH hypoactivity has been hypothesized 3,8±11 though a pituitary impairment due to metabolic alterations can not be ruled out.…”

Section: Introductionmentioning

confidence: 99%

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Maximal secretory capacity of somatotrope cells in obesity: comparison with GH deficiency

et al. 1997

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OBJECTIVE: To evaluate the maximal secretory capacity of somatotrope cells in obesity and to compare it with that in hypopituitaric patients with GH de®ciency. DESIGN: Stimulation with GHRH. (1 mg/kg iv) combined with arginine (ARG, 0.5 g/kg iv), which strongly potentiates the GH response to the neurohormone, likely inhibiting hypothalamic somatostatin. The reproducibility of the GH response to GHRH ARG was evaluated in a second session. SUBJECTS: Forty-®ve patients with simple obesity (OB 11 male and 34 female, age 40.5 AE AE 1.8 y, BMI 38.8 AE AE 1.1 kg/m 2 ), 49 patients with hypopituitarism (GHD, 23 male and 26 female, 43.6 AE AE 2.4 y, 24.7 AE AE 0.7 kg/m 2 ) and 44 normal young volunteers (NS, 25 male and 19 female, 33.8 AE AE 1.0 y, 21.6 AE AE 0.3 kg/m 2 ) were studied. MEASUREMENTS: GH levels were assayed by IRMA method, basally at 7 60 and 0 min, and than every 15 min up to 120 min. Basal IGF±I levels were assayed by RIA method, after acid-ethanol extraction. RESULTS: IGF±I levels in OB were lower (P`0.005) than those in NS but higher (P`0.005) than those in GHD. Mean peak GH response to GHRH ARG in OB was clearly lower than that in NS (P`0.005) and higher (P`0.005) than that in GHD. Sixty±percent OB and 100% GHD showed peak GH responses lower than the minimum normal limit in NS (16.5 mg/l) while 4% OB and only 53% GHD with GH responses lower than 3 mg/l, the limit under which GH replacement therapy of severe de®ciency is allowed. Good intraindividual reproducibility of the GH response to GHRH arginine test was present in all groups (OB: r 0.78, P`0.0001; GHD: r 0.57, P`0.003; NS: r 0.74, P`0.0001;. CONCLUSIONS: The maximal secretory capacity of somatotrope cells is clearly less than normal in the obese but still more than is seen in GHD subjects. However, in about 50% of obese patients, the pituitary GH releasable pool overlaps with that of hypopituitaric patients with GH de®ciency. Thus, even when the maximal secretory capacity of somatotrope cells is evaluated by a potent and reproducible provocative tests such as GHRH arginine, overweight has to be taken in a great account as the cause of severely impaired GH response in patients with suspected GH de®ciency.

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“…116 On the contrary, signi®cant weight reduction is associated, in these patients, with the restoration of a normal stimulated (GHRH, insulin-induced hypoglycaemia, arginine, L-dopa) and spontaneous GH secretion. 22,117,118 The high GHBP levels, consistently documented in obese subjects, normalise after signi®cant weight loss, whereas they are unchanged after short-term dietary restriction. 46,119 Changes in waist circumference and abdominal sagittal diameter during weight loss were the major determinants and accounted for 54% of the GH in obesity M Scacchi et al 264 fall in GHBP levels in a group of obese subjects submitted to a very low calorie diet.…”

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confidence: 99%

Growth hormone in obesity

1999

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Growth hormone (GH) secretion, either spontaneous or evoked by provocative stimuli, is markedly blunted in obesity. In fact obese patients display, compared to normal weight subjects, a reduced half-life, frequency of secretory episodes and daily production rate of the hormone. Furthermore, in these patients GH secretion is impaired in response to all traditional pharmacological stimuli acting at the hypothalamus (insulin-induced hypoglycaemia, arginine, galanin, L-dopa, clonidine, acute glucocorticoid administration) and to direct somatotrope stimulation by exogenous growth hormone releasing hormone (GHRH). Compounds thought to inhibit hypothalamic somatostatin (SRIH) release (pyridostigmine, arginine, galanin, atenolol) consistently improve, though do not normalize, the somatotropin response to GHRH in obesity. The synthetic growth hormone releasing peptides (GHRPs) GHRP-6 and hexarelin elicit in obese patients GH responses greater than those evoked by GHRH, but still lower than those observed in lean subjects. The combined administration of GHRH and GHRP-6 represents the most powerful GH releasing stimulus known in obesity, but once again it is less effective in these patients than in lean subjects. As for the peripheral limb of the GH ± insulin-like growth factor I (IGF-I) axis, high free IGF-I, low IGF-binding proteins 1 (IGFBP-1) and 2 (IGFBP-2), normal or high IGFBP-3 and increased GH binding protein (GHBP) circulating levels have been described in obesity. Recent evidence suggests that leptin, the product of adipocyte speci®c ob gene, exerts a stimulating effect on GH release in rodents; should the same hold true in man, the coexistence of high leptin and low GH serum levels in human obesity would ®t in well with the concept of a leptin resistance in this condition. Concerning the in¯uence of metabolic and nutritional factors, an impaired somatotropin response to hypoglycaemia and a failure of glucose load to inhibit spontaneous and stimulated GH release are well documented in obese patients; furthermore, drugs able to block lipolysis and thus to lower serum free fatty acids (NEFA) signi®cantly improve somatotropin secretion in obesity. Caloric restriction and weight loss are followed by the restoration of a normal spontaneous and stimulated GH release. On the whole, hypothalamic, pituitary and peripheral factors appear to be involved in the GH hyposecretion of obesity. A SRIH hypertone, a GHRH de®ciency or a functional failure of the somatotrope have been proposed as contributing factors. A lack of the putative endogenous ligand for GHRP receptors is another challenging hypothesis. On the peripheral side, the elevated plasma levels of NEFA and free IGF-I may play a major role. Whatever the cause, the defect of GH secretion in obesity appears to be of secondary, probably adaptive, nature since it is completely reversed by the normalization of body weight. In spite of this, treatment with biosynthetic GH has been shown to improve the body composition and the metabolic ef®cacy of lean body mass in obese pa...

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Very-low-calorie diet-induced weight reduction reverses impaired growth hormone secretion response to growth hormone-releasing hormone, arginine, and l-dopa in obesity

Cited by 60 publications

References 29 publications

Evaluation of pre- and postprandial growth hormone (GH)-releasing hormone-induced GH response in subjects with persistent body weight normalisation after biliopancreatic diversion

Evaluation of pre- and postprandial growth hormone (GH)-releasing hormone-induced GH response in subjects with persistent body weight normalisation after biliopancreatic diversion

Maximal secretory capacity of somatotrope cells in obesity: comparison with GH deficiency

Growth hormone in obesity

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