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Glucocorticoid inhibition of growth in rats: partial reversal with the full-length ghrelin analog BIM-28125

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Abstract

Glucocorticoids are important immunosuppressive hormones; these steroids also inhibit somatic growth by decreased growth hormone (GH) secretion and induced protein catabolism. The ability of ghrelin, the endogenous ligand for the GHS-1a receptor, to increase body weight is attributed to a combination of enhanced food intake, increased gastric emptying and increased food assimilation, coupled with potent GH releasing activity. The aim of the present study was to evaluate the ability of a full-length, metabolically stabilized ghrelin agonist, BIM-28125, to reverse the dexamethasone-induced decrease of growth rate of prepubertal Sprague–Dawley male rats. Twenty-one days old rats were randomly assigned to two treatment groups. Beginning on day 23 of age, 16 animals were treated ip either with saline or DEX (40 μg/kg/day). On day 33 after birth, these two groups were further subdivided and treated sc with either vehicle or BIM-28125 (80 nmol/kg, t.i.d.). On day 47 after birth, rats were killed and trunk blood was collected for hormone determinations. DEX significantly reduced final body weight and nose-anal length; BIM-28125 increased linear growth in saline-treated rats and reversed growth inhibition in DEX-treated rats. The inhibitory effects of DEX on somatic growth was paralleled by decreased 24 h food intake (FI), decreased food efficiency (FE) and lower plasma IGF-1 levels versus vehicle-treated rats. BIM-28125 induced an increase of FI, FE and plasma IGF-1 in saline-treated rats, and reversed the inhibitory effects of DEX. These preclinical results leads to the conclusion that BIM-28125 may represent a good tool to reverse the catabolic effects induced by glucocorticoids.

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Acknowledgements

This research was supported by Grants (60% 2005) from University of Brescia to Prof. Andrea Giustina and Prof. Daniela Cocchi (Brescia, Italy).

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Authors and Affiliations

  1. Department of Biomedical Sciences and Biotechnologies, University of Brescia, Brescia, Italy

    Giovanni Tulipano, Irene Bianchi & Daniela Cocchi

  2. IPSEN, Milford, MA, USA

    John E. Taylor, Heather A. Halem, Rakesh Datta, Jesse Z. Dong & Michael D. Culler

  3. Department of Internal Medicine, University of Brescia, Brescia, Italy

    Andrea Giustina

  4. Department of Internal Medicine (II), Spedali Civili di Brescia, 25123, Brescia, Italy

    Andrea Giustina

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  1. Giovanni Tulipano
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  2. John E. Taylor
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  3. Heather A. Halem
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  4. Rakesh Datta
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  5. Jesse Z. Dong
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  6. Michael D. Culler
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  7. Irene Bianchi
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  8. Daniela Cocchi
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  9. Andrea Giustina
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Correspondence to Andrea Giustina.

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Tulipano, G., Taylor, J.E., Halem, H.A. et al. Glucocorticoid inhibition of growth in rats: partial reversal with the full-length ghrelin analog BIM-28125. Pituitary 10, 267–274 (2007). https://doi.org/10.1007/s11102-007-0054-6

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  • DOI: https://doi.org/10.1007/s11102-007-0054-6

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