The GH/IGF-1 axis in obesity: pathophysiology and therapeutic considerations

Berryman, Darlene E.; Glad, Camilla A M; List, Edward O.; Johannsson, Gudmundur

doi:10.1038/nrendo.2013.64

Cited by 187 publications

(134 citation statements)

References 132 publications

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“…CBG = corticosteroidbinding globulin. Berryman et al, 2013). Several clinical studies have shown a relationship between CBG levels or CBG gene polymorphisms and metabolic parameters related to insulin resistance syndrome (e.g.…”

Section: Discussionmentioning

confidence: 99%

The cortisol response to ACTH in pigs, heritability and influence of corticosteroid-binding globulin

Larzul

Terenina

Foury

et al. 2015

Animal

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In the search for biological basis of robustness, this study aimed (i) at the determination of the heritability of the cortisol response to ACTH in juvenile pigs, using restricted maximum likelihood methodology applied to a multiple trait animal model, and (ii) at the study of the relationships between basal and stimulated cortisol levels with corticosteroid-binding globulin (CBG), IGF-I and haptoglobin, all important players in glucose metabolism and production traits. At 6 weeks of age, 298 intact male and female piglets from 30 litters (30 dams and 30 boars) were injected with 250 µg ACTH(1-24) (Synacthen). Blood was taken before ACTH injection to measure basal levels of cortisol, glucose, CBG, IGF-I and haptoglobin, and 60 min later to measure stimulated cortisol levels and glucose. Cortisol increased 2.8-fold after ACTH injection, with a high correlation between basal and stimulated levels (phenotypic correlation, r p = 0.539; genetic correlation, r g = 0.938). Post-ACTH cortisol levels were highly heritable ( h 2 = 0.684) and could therefore be used for genetic selection of animals with a more reactive hypothalamic-pituitary-adrenocortical axis. CBG binding capacity correlated with cortisol levels measured in basal conditions in males only. No correlation was found between CBG binding capacity and post-ACTH cortisol levels. Basal IGF-I concentration was positively correlated with BW at birth and weaning, and showed a high correlation with CBG binding capacity with a strong sexual dimorphism, the correlation being much higher in males than in females. Basal haptoglobin concentrations were negatively correlated with CBG binding capacity and IGF-I concentrations. Complex relationships were also found between circulating glucose levels and these different variables that have been shown to be related to glucose resistance in humans. These data are therefore valuable for the genetic selection of animals to explore the consequences on production and robustness traits, but also point at pigs as a relevant model to explore the underlying mechanisms of the metabolic syndrome including the contribution of genetic factors.

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Section: Discussionmentioning

confidence: 99%

The cortisol response to ACTH in pigs, heritability and influence of corticosteroid-binding globulin

Larzul

Terenina

Foury

et al. 2015

Animal

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“…There have been over 20 clinical trials with GH or GHSs in obesity but its efficacy remains to be established, and there are concerns around hyperglycaemic side effects (Berryman et al 2013). …”

Section: External Regulators Of the Central Gh Axismentioning

confidence: 99%

60 YEARS OF NEUROENDOCRINOLOGY: The hypothalamo-GH axis: the past 60 years

Murray¹,

Higham²,

Clayton³

2015

Journal of Endocrinology

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At the time of the publication of Geoffrey Harris's monograph on 'Neural control of the pituitary gland' 60 years ago, the pituitary was recognised to produce a growth factor, and extracts administered to children with hypopituitarism could accelerate growth. Since then our understanding of the neuroendocrinology of the GH axis has included identification of the key central components of the GH axis: GH-releasing hormone and somatostatin (SST) in the 1970s and 1980s and ghrelin in the 1990s. Characterisation of the physiological control of the axis was significantly advanced by frequent blood sampling studies in the 1980s and 1990s; the pulsatile pattern of GH secretion and the factors that influenced the frequency and amplitude of the pulses have been defined. Over the same time, spontaneously occurring and targeted mutations in the GH axis in rodents combined with the recognition of genetic causes of familial hypopituitarism demonstrated the key factors controlling pituitary development. As the understanding of the control of GH secretion advanced, developments of treatments for GH axis disorders have evolved. Administration of pituitary-derived human GH was followed by the introduction of recombinant human GH in the 1980s, and, more recently, by long-acting GH preparations. For GH excess disorders, dopamine agonists were used first followed by SST analogues, and in 2005 the GH receptor blocker pegvisomant was introduced. This review will cover the evolution of these discoveries and build a picture of our current understanding of the hypothalamo-GH axis.

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“…In addition to improving linear growth, GH exerts profound metabolic actions promoting anabolic effects and fat lipolysis (2). Although these actions contribute to the regulation of growth and metabolism, they may be associated with adverse effects when GH is in excess (3).…”

Section: Introductionmentioning

confidence: 99%