Effects of growth hormone and IGF-I on glucocorticoid-induced protein catabolism in humans

Oehri, M.; Ninnis, Ronald; Girard, J.; Frey, F J; Keller, Ulrich

doi:10.1152/ajpendo.1996.270.4.e552

Cited by 16 publications

(22 citation statements)

References 4 publications

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“…The enhanced anti-catabolic outcome with early IGF-I treatment may also allow the use of lower doses of IGF-I, which could minimise the suppression of growth hormone and insulin secretion (e.g. Oehri et al 1996) and development of clinical side effects ( Jabri et al 1994, Thompson et al 1995. A recent report by Butterfield et al (1997) has shown that IGF treatment in old women had anabolic effects on whole body and muscle protein synthesis rates consistent with our observations in the old-rat model.…”

Section: Experimental Treatmentsupporting

confidence: 88%

The anti-catabolic efficacy of insulin-like growth factor-I is enhanced by its early administration to rats receiving dexamethasone

Fürst

1998

Journal of Endocrinology

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The anti-catabolic efficacy of IGF-I treatment commencing before, with or after the onset of catabolism was compared in order to test whether earlier treatment can more effectively blunt a catabolic response. Young rapidly growing male rats (145 g body weight) and old weightstable female rats (270 g body weight) were used in two experiments. The IGF-I variant LR 3 IGF-I was continuously infused at 280 µg/day from 2 days before (early), concurrent with or 2 days after (delayed) commencement of a 6 day dexamethasone infusion (125 µg/kg per day).Both early and delayed treatment of young rats with LR 3 IGF-I significantly reduced the measured catabolic effects of dexamethasone. Early treatment was more effective than delayed treatment, with significantly higher nitrogen balance (90 12 vs 31 6 mg/day), carcass nitrogen gain (0·37 0·27 vs 1·13 0·10% per day) and protein fractional synthesis rates after 2 (10·4 0·5 vs 8·3 0·2% per day) and 6 days of dexamethasone (8·2 0·6 vs 7·0 0·3% per day). Similarly, fractional breakdown rates of carcass protein were maintained at significantly lower levels in rats given early treatment (6·23 0·24 vs 6·60 0·22% per day). In contrast, the old rats were less responsive to LR 3 IGF-I treatment and only early and concurrent treatment significantly reduced the catabolic response, partly because of higher food intake. Early treatment was superior to delayed treatment and led to significantly higher nitrogen balance ( 19 11 vs 83 7 mg/day) and carcass nitrogen fractional gain ( 1·19 0·40 vs 2·76 0·37% per day) as well as lower final rates of carcass protein fractional breakdown (3·55 0·15 vs 3·83 0·07% per day).These experiments show that early (prophylactic) treatment with IGF-I is superior to delayed treatment for reducing catabolism induced by dexamethasone. The results provide the basis for further research to determine if prophylactic IGF-I treatment is useful in other circumstances where catabolism can be anticipated, such as in elective major surgery.

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Section: Experimental Treatmentsupporting

confidence: 88%

The anti-catabolic efficacy of insulin-like growth factor-I is enhanced by its early administration to rats receiving dexamethasone

Fürst

1998

Journal of Endocrinology

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“…IGF-1 is an anabolic peptide and promotes growth not only by increasing proliferation, cell survival, and protein synthesis but also by decreasing protein breakdown. 25,[41][42][43] In models of catabolism, such as fasting, 44 burn injury, 45 and glucocorticoid treatment, 26 IGF-1 treatment decreases mRNA abundance of components of the Ub-pathway and therefore the Ub-proteasome pathway is considered as a mediator of the anti-proteolytic actions of IGF-1. Furthermore, IGF-1 is known to down-regulate the expression of the ubiquitin ligases atrogin-1 and MuRF-1, both important in skeletal muscle for the targeting of proteins to be degraded through the Ub-pathway.…”

Section: Discussionmentioning

confidence: 99%

Insulin-like growth factor-1 restores dexamethasone-induced heart growth arrest in rats: the role of the ubiquitin pathway

Chrysis¹,

Chagin²,

Sävendahl³

2011

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ObjEctIvE: In skeletal muscle, glucocorticoids induce catabolism and proteolysis which is accomplished via the ubiquitin (Ub) proteolytic pathway. cardiac muscle is a striated muscle which, compared to skeletal muscle, more abundantly expresses components of the Ub pathway, thus suggesting an important role for this pathway in heart physiology. the aim of our study was to explore the role of the Ub pathway in heart muscle physiology. DEsIGN: We treated rats for three days with a pharmacologic dose of dexamethasone (DEXA) 0.5mg/100g body weight (bW). An attempt was also made to counteract the DEXA effect by co-treatment with insulinlike growth factor-1 (IGF-1; 0.35mg/100g bW). rEsULts: DEXA treatment caused a 7.8% decrease in heart weight compared to control (p<0.05) and also increased heart tissue levels of the ubiquitin-conjugating enzyme E2 and the 20s proteasome protein. Myofibrillar proteins degraded by the ubiquitin pathway (α-actin, myoglobin, and troponin 1) were all decreased by DEXA, while ubiquitinated forms of α-actin were increased. Co-treatment with IGF-1 completely prevented DEXA-induced decrease in heart weight, an effect which was accompanied by decreased heart tissue levels of several ubiquitinated proteins including α-actin, the 20S proteasome protein, E2-14kDa mrNA, and c-3 proteasome subunit mrNA, while the levels of non-ubiquinated α-actin, myoglobin, and troponin 1 were all partially restored. CONCLUSION: these results demonstrate that DEXA activates the ubiquitin proteolytic pathway in the heart and that IGF-1 efficiently counteracts this effect. Our findings reveal a possible mechanism for the anti-proteolytic actions of IGF-1 and its cardioprotective role involving the Ub pathway.

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“…Urinary hydroxyproline was measured by a modified spectrophotometric assay (Woessner 1961, Podenphant et al 1984 and urinary pyridinoline and deoxypyridinoline by reverse-phase ion-paired HPLC (Seibel et al 1989, Black et al 1989. Serum total IGF-I and GH were measured as described previously (Oehri et al 1996).…”

Section: Methodsmentioning

confidence: 99%

Effects of IGF-I combined with GH on glucocorticoid-induced changes of bone and connective tissue turnover in man

Berneis

Oehri²,

Kraenzlin³

et al. 1999

Journal of Endocrinology

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Chronic glucocorticoid therapy results in negative bone and connective tissue balance. To assess the effects of GH and a combination of IGF-I and GH, 24 healthy male volunteers received in a double blind fashion either recombinant human GH (0·3 IU/kg per day s.c.), or a combination of GH (0·3 IU/kg per day s.c.) and IGF-I (80 µg/kg per day s.c.) or placebo (saline s.c.) during 6 days of methylprednisolone (0·5 mg/kg per day) treatment. Methylprednisolone decreased serum osteocalcin concentrations during placebo treatment from 32·9 2·1 to 9·0 1·4 µg/l (P<0·0001), indicating diminished osteoblast activity, and procollagen type I (PICP) and procollagen type III (PIIINP) to 46 and 70% of baseline respectively (P<0·005), indicating diminished bone (PICP) and soft tissue collagen synthesis (PIIINP). Urinary excretion of pyridinoline, deoxypyridinoline and hydroxyproline increased during treatment with methylprednisolone alone, indicating increased bone resorption (P<0·05 or less). The combination of GH and IGF-I resulted in a significant blunting of the methylprednisolone effect on serum PICP and PIIINP concentrations (P<0·005 or less vs placebo); this effect was in part due to IGF-I, since serum PICP concentrations decreased less in the combination group than during GH treatment alone (P<0·05). In the groups receiving GH and GH combined with IGF-I, urinary hydroxyproline excretion increased more when compared with methylprednisolone alone (P<0·05 or less).These findings demonstrate that only the combination of GH and IGF-I, but not GH alone, markedly counteracts diminished bone and body collagen synthesis caused by glucocorticoids, whereas connective tissue resorption is enhanced during treatment with GH alone and in combination with IGF-I.

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Effects of growth hormone and IGF-I on glucocorticoid-induced protein catabolism in humans

Cited by 16 publications

References 4 publications

The anti-catabolic efficacy of insulin-like growth factor-I is enhanced by its early administration to rats receiving dexamethasone

The anti-catabolic efficacy of insulin-like growth factor-I is enhanced by its early administration to rats receiving dexamethasone

Insulin-like growth factor-1 restores dexamethasone-induced heart growth arrest in rats: the role of the ubiquitin pathway

Effects of IGF-I combined with GH on glucocorticoid-induced changes of bone and connective tissue turnover in man

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