GH activity and markers of inflammation: a crossover study in healthy volunteers treated with GH and a GH receptor antagonist

Andreassen, Mikkel; Frystyk, Jan; Faber, Jens; Kristensen, Lars Østergaard

doi:10.1530/eje-11-1009

Cited by 33 publications

(33 citation statements)

References 60 publications

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“…Earlier studies showed that, after injection, GH and GHRH up-regulate TNF-α, IL1-α/β, and IL-6 in human blood (38) and in cells incubated with GH or GHRH (36,37). Last, the GHRH-R antagonist may inhibit the migration of immune cells into the aqueous humor, as suggested by the presence of GHRH-R only on cells in the aqueous humor but not in the stroma of the iris.…”

Section: Discussionmentioning

confidence: 98%

“…The GHRH-R antagonist JMR-132 can suppress the activation of Akt-kinase and ERK-kinase and reduce production of GHRH, thus inhibiting the growth of human androgen-independent prostate cancer (35). However, IGF1 also prevents the degradation of IκB and diminishes NF-κB translocation into the nucleus (36), leaving inconclusive IGF1's role as a pro-or anti-inflammatory agent (37). In this study we show that suppressing IGF1 production by blocking GHRH signaling alleviates inflammatory responses in ocular tissues.…”

Section: Discussionmentioning

confidence: 99%

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Antagonist of GH-releasing hormone receptors alleviates experimental ocular inflammation

Qin¹,

Chan

Chong

et al. 2014

Proc. Natl. Acad. Sci. U.S.A.

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Disruptions in immunity and occurrence of inflammation cause many eye diseases. The growth hormone-releasing hormone-growth hormone-insulin-like growth factor-1 (GHRH-GH-IGF1) axis exerts regulatory effects on the immune system. Its involvement in ocular inflammation remains to be investigated. Here we studied this signaling in endotoxin-induced uveitis (EIU) generated by LPS. The increase in GHRH receptor (GHRH-R) protein levels was parallel to the increase in mRNA levels of pituitary-specific transcription factor-1, GHRH-R splice variant 1, GHRH, and GH following LPS insult. Elevation of GHRH-R and GH receptor was localized on the epithelium of the iris and ciliary body, and GHRH-R was confined to the infiltrating macrophages and leukocytes in aqueous humor but not to those in stroma. Treatment with GHRH-R antagonist decreased LPS-stimulated surges of GH and IGF1 in aqueous humor and alleviated inflammation by reducing the infiltration of macrophages and leukocytes and the production of TNF-α, IL-1β, and monocyte chemotactic protein-1. Our results indicate that inflammation in the iris and ciliary body involves the activation of GHRH signaling, which affects the recruitment of immune cells and the production of proinflammatory mediators that contribute to EIU pathogenesis. Moreover, the results suggest that GHRH-R antagonists are potential therapeutic agents for the treatment of acute ocular inflammation.

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Section: Discussionmentioning

confidence: 98%

Section: Discussionmentioning

confidence: 99%

Antagonist of GH-releasing hormone receptors alleviates experimental ocular inflammation

Qin¹,

Chan

Chong

et al. 2014

Proc. Natl. Acad. Sci. U.S.A.

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“…(1) For direct effects on bone, there was increasing evidence that the GH-IGF axis played a vital role in determining BMD and maintaining bone health and that perturbations in this axis might predispose to the development of osteoporosis. Although GH could act on cells directly through specific receptors [31, 32], most of its anabolic actions were mediated through IGF-1 [33–35]. GH stimulated the secretion of IGF-1, largely from the liver, which then acted in an endocrine fashion.…”

Section: Discussionmentioning

confidence: 99%

Effects of Growth Hormone Replacement Therapy on Bone Mineral Density in Growth Hormone Deficient Adults: A Meta-Analysis

Xue

Wang

Yang

et al. 2013

International Journal of Endocrinology

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Objectives. Growth hormone deficiency patients exhibited reduced bone mineral density compared with healthy controls, but previous researches demonstrated uncertainty about the effect of growth hormone replacement therapy on bone in growth hormone deficient adults. The aim of this study was to determine whether the growth hormone replacement therapy could elevate bone mineral density in growth hormone deficient adults. Methods. In this meta-analysis, searches of Medline, Embase, and The Cochrane Library were undertaken to identify studies in humans of the association between growth hormone treatment and bone mineral density in growth hormone deficient adults. Random effects model was used for this meta-analysis. Results. A total of 20 studies (including one outlier study) with 936 subjects were included in our research. We detected significant overall association of growth hormone treatment with increased bone mineral density of spine, femoral neck, and total body, but some results of subgroup analyses were not consistent with the overall analyses. Conclusions. Our meta-analysis suggested that growth hormone replacement therapy could have beneficial influence on bone mineral density in growth hormone deficient adults, but, in some subject populations, the influence was not evident.

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“…Growth hormone given to healthy volunteers slightly but significantly increased serum TNF and serum IL-6 [118]. Growth hormone was made responsible for the chronic smoldering inflammation during aging, which can be studied in growth hormone pathway-deficient mice that demonstrate less inflammation and increased longevity [119].…”

Section: Hormone Effects On Inflammation and Observed Changes In Chromentioning

confidence: 99%

Interaction of the endocrine system with inflammation: a function of energy and volume regulation

Straub

2014

Arthritis Res Ther

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During acute systemic infectious disease, precisely regulated release of energy-rich substrates (glucose, free fatty acids, and amino acids) and auxiliary elements such as calcium/phosphorus from storage sites (fat tissue, muscle, liver, and bone) are highly important because these factors are needed by an energy-consuming immune system in a situation with little or no food/water intake (sickness behavior). This positively selected program for short-lived infectious diseases is similarly applied during chronic inflammatory diseases. This review presents the interaction of hormones and inflammation by focusing on energy storage/expenditure and volume regulation. Energy storage hormones are represented by insulin (glucose/lipid storage and growth-related processes), insulin-like growth factor-1 (IGF-1) (muscle and bone growth), androgens (muscle and bone growth), vitamin D (bone growth), and osteocalcin (bone growth, support of insulin, and testosterone). Energy expenditure hormones are represented by cortisol (breakdown of liver glycogen/adipose tissue triglycerides/muscle protein, and gluconeogenesis; water retention), noradrenaline/adrenaline (breakdown of liver glycogen/adipose tissue triglycerides, and gluconeogenesis; water retention), growth hormone (glucogenic, lipolytic; has also growth-related aspects; water retention), thyroid gland hormones (increase metabolic effects of adrenaline/noradrenaline), and angiotensin II (induce insulin resistance and retain water). In chronic inflammatory diseases, a preponderance of energy expenditure pathways is switched on, leading to typical hormonal changes such as insulin/IGF-1 resistance, hypoandrogenemia, hypovitaminosis D, mild hypercortisolemia, and increased activity of the sympathetic nervous system and the renin-angiotensin-aldosterone system. Though necessary during acute inflammation in the context of systemic infection or trauma, these long-standing changes contribute to increased mortality in chronic inflammatory diseases.

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GH activity and markers of inflammation: a crossover study in healthy volunteers treated with GH and a GH receptor antagonist

Cited by 33 publications

References 60 publications

Antagonist of GH-releasing hormone receptors alleviates experimental ocular inflammation

Antagonist of GH-releasing hormone receptors alleviates experimental ocular inflammation

Effects of Growth Hormone Replacement Therapy on Bone Mineral Density in Growth Hormone Deficient Adults: A Meta-Analysis

Interaction of the endocrine system with inflammation: a function of energy and volume regulation

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