Glucocorticoid inhibition of growth in rats: partial reversal with the full-length ghrelin analog BIM-28125.
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 microg/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.
Tulipano
Giovanni
G
Department of Biomedical Sciences and Biotechnologies, University of Brescia, Brescia, Italy.
Taylor
John E
JE
Halem
Heather A
HA
Datta
Rakesh
R
Dong
Jesse Z
JZ
Culler
Michael D
MD
Bianchi
Irene
I
Cocchi
Daniela
D
Giustina
Andrea
A
D000273:Adipose Tissue / Q000187:drug effects / Q000254:growth & development; D000818:Animals; D001786:Blood Glucose / Q000378:metabolism; D016466:CHO Cells; D006224:Cricetinae; D003412:Cricetulus; D004305:Dose-Response Relationship, Drug; D004435:Eating / Q000187:drug effects; D004822:Epididymis / Q000187:drug effects / Q000254:growth & development; D054439:Ghrelin / Q000031:analogs & derivatives* / Q000494:pharmacology; D005938:Glucocorticoids / Q000037:antagonists & inhibitors* / Q000494:pharmacology*; D006128:Growth / Q000187:drug effects*; D006727:Hormone Antagonists / Q000494:pharmacology*; D006801:Humans; D007334:Insulin-Like Growth Factor I / Q000378:metabolism; D008297:Male; D009765:Obesity / Q000139:chemically induced / Q000473:pathology; D010716:Phosphatidylinositols / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D011986:Receptors, Somatotropin / Q000187:drug effects; D011994:Recombinant Proteins / Q000494:pharmacology
C527636:BIM-28125; D001786:Blood Glucose; D054439:Ghrelin; D005938:Glucocorticoids; D006727:Hormone Antagonists; D010716:Phosphatidylinositols; D011986:Receptors, Somatotropin; D011994:Recombinant Proteins; D007334:Insulin-Like Growth Factor I