Novel Relationships of Age, Visceral Adiposity, Insulin-Like Growth Factor (IGF)-I and IGF Binding Protein Concentrations to Growth Hormone (GH) Releasing-Hormone and GH Releasing-Peptide Efficacies in Men during Experimental Hypogonadal Clamp

Veldhuis, Johannes D.; Keenan, Daniel M.; Bailey, James; Adeniji, Adebordurin M.; Miles, John M.; Bowers, Cyril Y.

doi:10.1210/jc.2009-0136

Cited by 7 publications

(5 citation statements)

References 39 publications

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“…In particular, AVF or TAF negatively predicted: (i) exercise-induced incremental GH secretion; (ii) the decrement in GH secretion imposed by iv glucose; and (iii) the rebound in GH secretion following transient glucose suppression. These insights complement earlier findings that AVF (or TAF) explains significant effects of age and gender on fasting/rest GH output in healthy subjects [22–25] and in patients with HIV lipidystrophy [26]. Whereas the precise bases for these negative effects of AVF are not known, obesity-associated factors like insulin and free fatty acids putatively suppress GH secretion, adiponectin and ghrelin amplify GH secretion, and leptin inhibits fasting-induced GH elevations [27, 28].…”

Section: Discussionsupporting

confidence: 89%

Multipathway modulation of exercise and glucose stress effects upon GH secretion in healthy men

Veldhuis¹,

Olson

Takahashi

et al. 2015

Metabolism

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Objective Exercise evokes pulsatile GH release followed by autonegative feedback, whereas glucose suppresses GH release followed by rebound-like GH release (feedforward escape). Here we test the hypothesis that age, sex steroids, insulin, body composition and physical power jointly determine these dynamic GH responses. Methods This was a prospectively randomized glucose-blinded study conducted in the Mayo Center for Advancing Translational Sciences in healthy men ages 19–77 yr (N = 23). Three conditions, fasting/rest/saline, fasting/exercise/saline and fasting/rest/iv glucose infusions, were used to drive GH dynamics during 10-min blood sampling for 6 hr. Linear correlation analysis was applied to relate peak/nadir GH dynamics to age, sex steroids, insulin, CT-estimated abdominal fat and physical power (work per unit time). Results Compared with the fasting/rest/saline (control) day, fasting/exercise/saline infusion evoked peak GH within 1 h, followed by negative feedback 3–5 h later. The dynamic GH excursion was strongly (R2 = 0.634) influenced by (i) insulin negatively (P = 0.011), (ii) power positively (P = 0.0008), and (iii) E2 positively (P = 0.001). Dynamic glucose-modulated GH release was determined by insulin negatively (P = 0.0039) and power positively (P = 0.0034) [R2 = 0.454]. Under rest/saline, power (P = 0.031) and total abdominal fat (P = 0.012) [R2 = 0.267] were the dominant correlates of GH excursions. Conclusion In healthy men, dynamic GH perturbations induced by exercise and glucose are strongly related to physical power, insulin, estradiol, and body composition, thus suggesting a network of regulatory pathways.

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Section: Discussionsupporting

confidence: 89%

Multipathway modulation of exercise and glucose stress effects upon GH secretion in healthy men

Veldhuis¹,

Olson

Takahashi

et al. 2015

Metabolism

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“…In a follow-up study, Veldhuis and colleagues assessed the effects of age, IGF-1 levels and AVF on GHRH and GHRP treatment response in 25 healthy men (43). All 25 men, including 13 young men and 12 older men, received two depot leuprolide acetate injections three weeks apart to create an acutely hypogonadal state.…”

Section: Ghrp-2 and Ghrp-6mentioning

confidence: 99%

Beyond the androgen receptor: the role of growth hormone secretagogues in the modern management of body composition in hypogonadal males

et al. 2020

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Male hypogonadism is an increasingly prevalent clinical condition that affects patients' quality of life and overall health. Obesity and metabolic syndrome can both cause and result from hypogonadism.Although testosterone remains the gold standard for hypogonadism management, its benefits are not always conserved across different populations, especially with regards to changes in body composition. Partially in response to this, growth hormone secretagogues (GHS) have emerged as a potential novel adjunctive therapy for some of the symptoms of hypogonadism, although current data on their clinical efficacy largely remain lacking. The present review examines the existing literature on the use of GHS and explores their potential complementary role in the management of hypogonadal and eugonadal males with metabolic syndrome or subclinical hypogonadism (SH). The GHS that will be discussed include sermorelin, growth hormone-releasing peptides (GHRP)-2, GHRP-6, ibutamoren, and ipamorelin. All are potent GH and IGF-1 stimulators that can significantly improve body composition while ameliorating specific hypogonadal symptoms including fat gain and muscular atrophy. However, a paucity of data examining the clinical effects of these compounds currently limits our understanding of GHS' role in the treatment of men with hypogonadism, but does open opportunities for future investigation.

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“…[100][101][102][103][104] In young women, oestrogen availability and visceral fat mass determine pulsatile GH secretion, 105 whereas in older men, visceral fat and pulsatile GH action account for half of the variability in the efficacies of GHRH or GHRP-2 under conditions of sex-steroid depletion. 106 A family of 6 high-affinity IGFBPs is of key importance in regulating the circulating half-life of IGFs and influences the spectrum of IGF activities in tissues. One of these, IGFBP-1, is secreted by hepatocytes under transcriptional inhibition by insulin and blocks the actions of 'free' IGFs, not bound in a ternary complex with IGFBP-3 or IGFBP-5 and a third ALS in a range of peripheral tissues.…”

Section: Gh/igf System and Vatmentioning

confidence: 99%

“…100–104 In young women, oestrogen availability and visceral fat mass determine pulsatile GH secretion, 105 whereas in older men, visceral fat and pulsatile GH action account for half of the variability in the efficacies of GHRH or GHRP-2 under conditions of sex-steroid depletion. 106…”

Section: Gh/igf System and Vatmentioning

confidence: 99%

The Role of the Growth Hormone/Insulin-Like Growth Factor System in Visceral Adiposity

Lewitt

2017

Biochem Insights

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There is substantial evidence that the growth hormone (GH)/insulin-like growth factor (IGF) system is involved in the pathophysiology of obesity. Both GH and IGF-I have direct effects on adipocyte proliferation and differentiation, and this system is involved in the cross-talk between adipose tissue, liver, and pituitary. Transgenic animal models have been of importance in identifying mechanisms underlying these interactions. It emerges that this system has key roles in visceral adiposity, and there is a rationale for targeting this system in the treatment of visceral obesity associated with GH deficiency, metabolic syndrome, and lipodystrophies. This evidence is reviewed, gaps in knowledge are highlighted, and recommendations are made for future research.

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Novel Relationships of Age, Visceral Adiposity, Insulin-Like Growth Factor (IGF)-I and IGF Binding Protein Concentrations to Growth Hormone (GH) Releasing-Hormone and GH Releasing-Peptide Efficacies in Men during Experimental Hypogonadal Clamp

Cited by 7 publications

References 39 publications

Multipathway modulation of exercise and glucose stress effects upon GH secretion in healthy men

Multipathway modulation of exercise and glucose stress effects upon GH secretion in healthy men

Beyond the androgen receptor: the role of growth hormone secretagogues in the modern management of body composition in hypogonadal males

The Role of the Growth Hormone/Insulin-Like Growth Factor System in Visceral Adiposity

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