title: Dexamethasone and BCAA Failed to Modulate Muscle Mass and mTOR Signaling in GH-Deficient Rats.
abstract: Branched-chain amino acids (BCAAs) and IGF-I, the secretion of which is stimulated by growth hormone (GH), prevent muscle atrophy. mTOR plays a pivotal role in the protective actions of BCAA and IGF-1. The pathway by which BCAA activates mTOR is different from that of IGF-1, which suggests that BCAA and GH work independently. We tried to examine whether BCAA exerts a protective effect against dexamethasone (Dex)-induced muscle atrophy independently of GH using GH-deficient spontaneous dwarf rats (SDRs). Unexpectedly, Dex did not induce muscle atrophy assessed by the measurement of cross-sectional area (CSA) of the muscle fibers and did not increase atrogin-1, MuRF1 and REDD1 expressions, which are activated during protein degradation. Glucocorticoid (GR) mRNA levels were higher in SDRs compared to GH-treated SDRs, indicating that the low expression of GR is not the reason of the defect of Dex's action in SDRs. BCAA did not stimulate the phosphorylation of p70S6K or 4E-BP1, which stimulate protein synthesis. BCAA did not decrease the mRNA level of atrogin-1 or MuRF1. These findings suggested that Dex failed to modulate muscle mass and that BCAA was unable to activate mTOR in SDRs because these phosphorylations of p70S6K and 4E-BP1 and the reductions of these mRNAs are regulated by mTOR. In contrast, after GH supplementation, these responses to Dex were normalized and muscle fiber CSA was decreased by Dex. BCAA prevented the Dex-induced decrease in CSA. BCAA increased the phosphorylation of p70S6K and decreased the Dex-induced elevations of atrogin-1 and Bnip3 mRNAs. However, the amount of mTORC1 components including mTOR was not decreased in the SDRs compared to the normal rats. These findings suggest that GH increases mTORC1 activity but not its content to recover the action of BCAA in SDRs and that GH is required for actions of Dex and BCAA in muscles.
authors.affiliation: Department of Nutrition and Food Science, Kobe Women's University Graduate School of Life Sciences, Kobe, Japan.
authors.forename: Hikaru
authors.initials: H
authors.lastname: Nishida
authors.affiliation: Department of Nutrition and Food Science, Kobe Women's University Graduate School of Life Sciences, Kobe, Japan.
authors.forename: Ayaka
authors.initials: A
authors.lastname: Ikegami
authors.affiliation: Department of Nutrition and Food Science, Kobe Women's University Graduate School of Life Sciences, Kobe, Japan.
authors.forename: Chiaki
authors.initials: C
authors.lastname: Kaneko
authors.affiliation: Department of Nutrition and Food Science, Kobe Women's University Graduate School of Life Sciences, Kobe, Japan.
authors.forename: Hitomi
authors.initials: H
authors.lastname: Kakuma
authors.affiliation: Department of Nutrition and Food Science, Kobe Women's University Graduate School of Life Sciences, Kobe, Japan.
authors.forename: Hisano
authors.initials: H
authors.lastname: Nishi
authors.affiliation: Department of Nutrition and Food Science, Kobe Women's University Graduate School of Life Sciences, Kobe, Japan.
authors.forename: Noriko
authors.initials: N
authors.lastname: Tanaka
authors.affiliation: Division of Nutrition and Metabolism, Kobe University Graduate School of Health Sciences, Kobe, Japan.
authors.forename: Michiko
authors.initials: M
authors.lastname: Aoyama
authors.affiliation: Division of Nutrition and Metabolism, Kobe University Graduate School of Health Sciences, Kobe, Japan.
authors.forename: Makoto
authors.initials: M
authors.lastname: Usami
authors.affiliation: Department of Nutrition and Food Science, Kobe Women's University Graduate School of Life Sciences, Kobe, Japan.
authors.forename: Yasuhiko
authors.initials: Y
authors.lastname: Okimura
mesh_terms: D000597:Amino Acids, Branched-Chain / Q000494:pharmacology*; D000818:Animals; D003907:Dexamethasone / Q000494:pharmacology*; D005938:Glucocorticoids / Q000494:pharmacology*; D013006:Growth Hormone / Q000172:deficiency* / Q000494:pharmacology / Q000502:physiology; D018485:Muscle Fibers, Skeletal / Q000187:drug effects; D009133:Muscular Atrophy / Q000139:chemically induced* / Q000209:etiology / Q000517:prevention & control; D051381:Rats; D011922:Rats, Mutant Strains; D017207:Rats, Sprague-Dawley; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology; D058570:TOR Serine-Threonine Kinases / Q000187:drug effects / Q000502:physiology*
chemical_list: D000597:Amino Acids, Branched-Chain; D005938:Glucocorticoids; D003907:Dexamethasone; D013006:Growth Hormone; C546845:mTOR protein, rat; D058570:TOR Serine-Threonine Kinases