Inhibition by Prednisone of Growth Hormone (GH) Response to GH-Releasing Hormone in Normal Men

Kaufmann, Silvia; Jones, Kathryn L.; Wehrenberg, William B.; Culler, Floyd L.

doi:10.1210/jcem-67-6-1258

Cited by 87 publications

(30 citation statements)

References 24 publications

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“…Carbohydrate metabolism can also be affected by prolonged steroid administration, causing insulin resistance to both hepatic and peripheral tissues, leading at times to frank carbohydrate intolerance [9]. When administered to growing children these side effects of GC treatment are compounded further by a potent and significant suppression of linear growth [10, 11, 12, 13]. Hence, the prevention or amelioration of some of these adverse events associated with chronic GC use could have important implications on the management of a wide variety of patients.…”

Section: Introductionmentioning

confidence: 99%

Growth Hormone Therapy in the Glucocorticosteroid-Dependent Child: Metabolic and Linear Growth Effects

Mauras

2001

Horm Res Paediatr

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Pharmacological doses of glucocorticosteroids given chronically are associated with a variety of negative side effects which impact the prolonged use of these potent anti-inflammatory agents. They have catabolic effects on protein, resulting in poor tissue healing, an increased incidence of infections and accelerated bone loss. Insulin resistance to both hepatic and peripheral tissues is a common consequence of chronic steroid use, leading at times to impaired carbohydrate metabolism. Steroids affect both the release and the effects of growth hormone (GH) at the target sites, hence becoming functional GH antagonists. When administered to growing children the side effects of glucocorticosteroid treatment are further compounded by a potent and significant suppression of linear growth. Ample experimental and clinical data support a role for GH therapy in counteracting some of the effects of glucocorticosteroids. Using isotope dilution methods we have previously shown that both GH and insulin-like growth factor (IGF)-I can decrease the protein wasting effects of prednisone administration in man. IGF-I has also been shown to enhance type I collagen formation in hydrocortisone-treated human osteoblasts. GH (through IGF-I) significantly enhances linear growth; thus, in states of ‘functional’ GH deficiency, such as that observed in chronic steroid use, GH may also have a potentially beneficial effect. Studies in children on chronic prednisone doses with cystic fibrosis, chronic renal failure or juvenile rheumatoid arthritis have all shown beneficial effects on linear growth after prolonged GH therapy. Data from a recent study of ours using GH in children with steroid-dependent inflammatory bowel disease showed that GH treatment was associated with increased lean body mass, decreased adiposity and increased linear growth. Marked increases in IGF-I concentrations and in kinetic measures of bone calcium accretion (using calcium tracers) were also observed, without any deterioration of disease activity scores or carbohydrate tolerance. In conclusion, GH therapy may play a role in the treatment of children on chronic steroids both as a growth promoting agent and as an anabolic agent on whole body protein and bone. Longer term studies will be needed to better define the safety and efficacy of this approach.

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Section: Introductionmentioning

confidence: 99%

Growth Hormone Therapy in the Glucocorticosteroid-Dependent Child: Metabolic and Linear Growth Effects

Mauras

2001

Horm Res Paediatr

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“…In humans administration of glucocorticoid has been shown to increase endogenous GH secretion [12, 14, 16, 26]whereas the effect of glucocorticoid administration on GH release during GH stimulation test are ambiguous as both blunted and enhanced responses have been reported [5, 6, 7]. During glucocorticoid exposure increased levels of IGF-I has frequently been described [1, 2, 5, 8, 11, 12, 13, 14, 15, 16], although some studies found no changes [9, 10, 17, 18].…”

Section: Discussionmentioning

confidence: 99%

“…Glucocorticoid administration in healthy adults has been shown to increase protein oxidation, which is prevented by co-administration of GH [1, 2, 3, 4]. The effects of hypercortisolaemia on GH release are, however, ambiguous as both blunted and enhanced responses to GH stimulation tests have been reported [5, 6, 7]. Moreover, serum total IGF-I concentrations are normal or even elevated after both short-term and more prolonged exposure to glucocorticoids [1, 2, 5, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18].…”

Section: Introductionmentioning

confidence: 99%

No Influence of Prednisolone on IGFBP-3 Proteolysis in Healthy Young Men

et al. 2001

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Aims: The impact of growth hormone (GH) and prednisolone on the GH/insulin-like growth factor (IGF) axis with special emphasis on IGF binding protein-3 (IGFBP-3) proteolysis was studied in 8 healthy adults in a double-blind cross-over study with four periods: (1) placebo; (2) s.c. GH 0.1 IU/kg/day; (3) oral prednisolone 50 mg/day, and (4) co-administration of GH and prednisolone. Methods: Each treatment period lasted for 4 days followed by a washout period of 10 days. We measured IGF-I, IGF-II, IGFBP-1, IGFBP-2, IGFBP-3 by immunoassays, IGFBP-3 by Western ligand blotting (WLB) and finally in vitro IGFBP-3 proteolysis by a ¹²⁵I-IGFBP-3 degradation assay. Results: IGF-I levels increased by 99% during GH administration and 67% during co-administration of GH and prednisolone (p < 0.0005), whereas no significant change was seen during prednisolone alone. IGFBP-1 levels decreased 55% during the prednisolone period (p < 0.002), but the between period changes were not significant (p < 0.1). IGFBP-2 decreased 33% during co-administration of GH and prednisolone (p < 0.002). IGFBP-3 increased 12% during GH and 7% during co-administration of GH and prednisolone (p < 0.003 and p < 0.03 compared to placebo, respectively), whereas prednisolone alone induced no significant changes. IGFBP-3 measured by WLB did not change significantly, neither did IGFBP-3 proteolysis. Conclusions: Prednisolone administration induces only minimal changes in circulating components of the IGF axis and is not accompanied by alterations in IGFBP-3 proteolysis. This indicates that the metabolic effects of glucocorticoids do not depend on serum IGF-I.

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“…The mechanism of linear growth inhibition by GC has not been defined. The findings regarding the effects of GC on GH secretion are controversial [4, 5, 6, 7, 8]. It appears that GC may affect not so much the level of GH secretion, but rather the nyctohemeral GH secretion profile, resulting in delayed and attenuated nocturnal GH secretion peaks [9].…”

Section: Discussionmentioning

confidence: 99%

Treatment of Juvenile Rheumatoid Arthritis with Growth Hormone

2000

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Severe growth retardation and profoundly altered body composition are observed in children with juvenile chronic arthritis receiving glucocorticoids. This study assessed the effects of growth hormone (GH) on height velocity, body composition and bone density. Fourteen patients were treated with GH (1.4 U/kg/week) for 1 year and then studied for a 2nd year off GH. The treatment increased insulin-like growth factor 1 and insulin-like growth factor binding protein 3 plasma levels. All patients showed an increase in height velocity. Lean body mass increased by 12%. After the cessation of GH therapy, height velocity fell to pretreatment values, and weight and fat mass increased markedly. Bone formation and resorption markers significantly increased during treatment and returned to pretreatment values after discontinuation of GH treatment. These results suggest that GH may partially counteract the adverse effects of glucocorticoids on growth and metabolism in patients with chronic inflammatory disease.

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Inhibition by Prednisone of Growth Hormone (GH) Response to GH-Releasing Hormone in Normal Men

Cited by 87 publications

References 24 publications

Growth Hormone Therapy in the Glucocorticosteroid-Dependent Child: Metabolic and Linear Growth Effects

Growth Hormone Therapy in the Glucocorticosteroid-Dependent Child: Metabolic and Linear Growth Effects

No Influence of Prednisolone on IGFBP-3 Proteolysis in Healthy Young Men

Treatment of Juvenile Rheumatoid Arthritis with Growth Hormone

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