title: Increased locomotor and thermogenic activity in mice with targeted ablation of the GHRH gene.
abstract: OBJECTIVE
  Growth hormone (GH) deficiency (GHD) leads to growth failure and changes in body composition, including increased fat accumulation and reduced lean body mass in both humans and rodents. The aim of this study was to examine the factors that contribute to energy imbalance in the GH releasing hormone knock out (GHRHKO) mice, a well established model of GHD.
  
  
  METHODS
  We evaluated food intake (of standard laboratory chow), total body weight (TBW), locomotor activity, body temperature and interscapular brown adipose tissue (BAT) weight in 8 adult male mice homozygous for the GHRHKO allele (-/-) and 8 heterozygous (+/-) animals as controls. The gene expression of uncoupling protein-1 (UCP-1) in BAT and the levels of norepinephrine (NE), dopamine (DA), and serotonin (5-hydroxytryptamine, 5-HT) in the ventral striatum were measured by real-time reverse transcription polymerase chain reaction (RT-PCR) and high performance liquid chromatography (HPLC) analysis, respectively.
  
  
  RESULTS
  Throughout 2 months of observation -/- mice consumed approximately 40% more food (normalized to TBW; P<0.001), and showed increased locomotor activity in 24h time compared to controls (P<0.05). Moreover, -/- animals showed increased body temperature (P<0.001), BAT weight (P<0.001), and UCP-1 gene expression (P<0.001), while NE levels in the striatum area were lower (P<0.05) than controls.
  
  
  CONCLUSIONS
  The present study demonstrates that the increased food intake observed in GHRH ablated animals is associated with increased locomotor and thermogenic activity.
authors.affiliation: Department of Pharmacy, G. d'Annunzio University, Chieti, Italy.
authors.forename: Sheila
authors.initials: S
authors.lastname: Leone
authors.affiliation: Department of Pharmacy, G. d'Annunzio University, Chieti, Italy.
authors.forename: Annalisa
authors.initials: A
authors.lastname: Chiavaroli
authors.affiliation: Department of Pharmacy, G. d'Annunzio University, Chieti, Italy.
authors.forename: Rugia
authors.initials: R
authors.lastname: Shohreh
authors.affiliation: Department of Pharmacy, G. d'Annunzio University, Chieti, Italy.
authors.forename: Claudio
authors.initials: C
authors.lastname: Ferrante
authors.affiliation: Department of Pharmacy, G. d'Annunzio University, Chieti, Italy.
authors.forename: Adriana
authors.initials: A
authors.lastname: Ricciuti
authors.affiliation: Department of Pharmacy, G. d'Annunzio University, Chieti, Italy.
authors.forename: Fabio
authors.initials: F
authors.lastname: Manippa
authors.affiliation: Department of Pharmacy, G. d'Annunzio University, Chieti, Italy.
authors.forename: Lucia
authors.initials: L
authors.lastname: Recinella
authors.affiliation: Department of Pharmacy, G. d'Annunzio University, Chieti, Italy.
authors.forename: Chiara
authors.initials: C
authors.lastname: Di Nisio
authors.affiliation: Department of Pharmacy, G. d'Annunzio University, Chieti, Italy.
authors.forename: Giustino
authors.initials: G
authors.lastname: Orlando
authors.affiliation: Department of Medicine, Division of Endocrinology, Diabetes and Metabolism, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
authors.forename: Roberto
authors.initials: R
authors.lastname: Salvatori
authors.affiliation: Department of Pharmacy, G. d'Annunzio University, Chieti, Italy.
authors.forename: Michele
authors.initials: M
authors.lastname: Vacca
authors.affiliation: Department of Pharmacy, G. d'Annunzio University, Chieti, Italy. Electronic address: brunetti@unich.it.
authors.forename: Luigi
authors.initials: L
authors.lastname: Brunetti
mesh_terms: D002001:Adipose Tissue, Brown / Q000033:anatomy & histology / Q000378:metabolism; D000818:Animals; D001831:Body Temperature / Q000235:genetics; D004435:Eating / Q000235:genetics; D005260:Female; D017353:Gene Deletion; D013007:Growth Hormone-Releasing Hormone / Q000235:genetics*; D007473:Ion Channels / Q000235:genetics / Q000378:metabolism; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D024101:Mitochondrial Proteins / Q000235:genetics / Q000378:metabolism; D009043:Motor Activity / Q000235:genetics*; D009929:Organ Size / Q000235:genetics; D022722:Thermogenesis / Q000235:genetics*; D000071256:Uncoupling Protein 1
chemical_list: D007473:Ion Channels; D024101:Mitochondrial Proteins; C000604371:UCP1 protein, human; C000604372:Ucp1 protein, mouse; D000071256:Uncoupling Protein 1; D013007:Growth Hormone-Releasing Hormone
keywords: Brown adipose tissue; Food intake; Growth hormone-releasing hormone; Locomotor activity; Norepinephrine; Uncoupling protein-1