Repetitive GHRH Administration Fails to Increase the Response to GHRH in Obese Subjects

Ghigo, Ezio; Procopio, Massimo; Maccario, Mauro; Bellone, J.; Arvat, E.; Campana, Steven E.; Mf, Boghen; Camanni, F.

doi:10.1055/s-2007-1002105

Cited by 24 publications

(10 citation statements)

References 25 publications

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“…On the other hand, also the existence of GHRH hypoactivity has been proposed in obesity; 8,39,40 this, in turn, could cause reduced GH synthesis and, thus, explain the reduction in the maximal secretory capacity of somatotrope cells and present data. 8,41 Other data, however, do not support the existence Figure 1 Mean ( s.e.m.)…”

Section: Discussionsupporting

confidence: 62%

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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Section: Discussionsupporting

confidence: 62%

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

et al. 1997

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“…Moreover, human and animal studies provide compelling evidence to suggest that the hypothalamus may not be the principle site for altered GH secretion in obesity. Hypothalamic gene expression for GHRH and somatostatin does not change in dietaryinduced obese rats, regardless of pituitary insensitivity to GHRH (Cattaneo et al 1996), while chronic GHRH treatment coupled with arginine (to suppress endogenous SRIF release) does not recover GH secretion in dietaryinduced obese patients (Ghigo et al 1993). Consequently, it seems that impairments of GH secretion in obesity occur independent of changes in hypothalamic control of GH secretion.…”

Section: Discussionmentioning

confidence: 93%

Increased adiposity and insulin correlates with the progressive suppression of pulsatile GH secretion during weight gain

Steyn

Xie

Huang

et al. 2013

Journal of Endocrinology

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Pathological changes associated with obesity are thought to contribute to GH deficiency. However, recent observations suggest that impaired GH secretion relative to excess calorie consumption contributes to progressive weight gain and thus may contribute to the development of obesity. To clarify this association between adiposity and GH secretion, we investigated the relationship between pulsatile GH secretion and body weight; epididymal fat mass; and circulating levels of leptin, insulin, non-esterified free fatty acids (NEFAs), and glucose. Data were obtained from male mice maintained on a standard or high-fat diet. We confirm the suppression of pulsatile GH secretion following dietary-induced weight gain. Correlation analyses reveal an inverse relationship between measures of pulsatile GH secretion, body weight, and epididymal fat mass. Moreover, we demonstrate an inverse relationship between measures of pulsatile GH secretion and circulating levels of leptin and insulin. The secretion of GH did not change relative to circulating levels of NEFAs or glucose. We conclude that impaired pulsatile GH secretion in the mouse occurs alongside progressive weight gain and thus precedes the development of obesity. Moreover, data illustrate key interactions between GH secretion and circulating levels of insulin and reflect the potential physiological role of GH in modulation of insulin-induced lipogenesis throughout positive energy balance. Key Words" pulsatile GH secretion " dietary-induced weight gain " insulin " non-esterified free fatty acids " adiposity

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“…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. 22 These ®ndings, however, do not de®nitively rule out the possibility that endogenous GHRH hypoactivity plays a critical role.…”

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confidence: 97%

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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Repetitive GHRH Administration Fails to Increase the Response to GHRH in Obese Subjects

Cited by 24 publications

References 25 publications

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

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

Increased adiposity and insulin correlates with the progressive suppression of pulsatile GH secretion during weight gain

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

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