title: GH signaling in skeletal muscle and adipose tissue in healthy human subjects: impact of gender and age.
abstract: OBJECTIVE
  The mechanisms underlying the impact of age and gender on the GH-IGF1 axis remain unclear. We tested the hypothesis that age and gender have impacts on GH signaling in human subjects in vivo.
  
  
  METHODS
  A total of 20 healthy non-obese adults ('young group'<30 years (5F/5M) and 'old group'>60 years (5F/5M)) were studied after: i) an i.v. GH bolus (0.5 mg) and ii) saline.
  
  
  METHODS
  Muscle and fat biopsies were obtained after 30 and 120 min. Total and phosphorylated STAT5B proteins, gene expression of IGF1, SOCS1, SOCS2, SOCS3 and CISH, body composition, VO2max, and muscle strength were measured.
  
  
  RESULTS
  In the GH-unstimulated state, women displayed significantly elevated levels of CISH mRNA in muscle (P=0.002) and fat (P=0.05) and reduced levels of IGF1 mRNA in fat. Phosphorylated STAT5B (pSTAT5b) was maximally increased in all subjects 30 min after GH exposure and more pronounced in women when compared with men (P=0.01). IGF1, SOCS1, SOCS2, SOCS3, and CISH mRNA expression increased significantly in muscle after 120 min in all subjects with no impact of age and gender. GH-induced pSTAT5b correlated inversely with lean body mass (LBM; r=-0.56, P=0.01) and positively with the CISH mRNA response (r=0.533, P=0.05).
  
  
  CONCLUSIONS
  i) GH signaling in muscle and fat after a single GH bolus in healthy human subjects is age independent, ii) we hypothesize that constitutive overexpression of CISH may contribute to the relative GH resistance in women, and iii) experimental studies on the impact of sex steroid administration and physical training on GH signaling in human subjects in vivo are required.
authors.affiliation: The Medical Research LaboratoriesDepartment of Endocrinology and Internal Medicine, Faculty of Health Sciences, Institute of Clinical Medicine, Aarhus University Hospital, Aarhus University, Nørrebrogade 44, DK-8000 Aarhus C, DenmarkDepartment of Growth and ReproductionUniversity Hospital of Copenhagen, Rigshospitalet, Blegdamsvej 9, 2100 Copenhagen Ø, DenmarkDepartment of Clinical MedicineMR Research Centre Aarhus University Hospital, Skejby, Brendstrupgaardsvej 100, DK-8200 Aarhus N, Denmark poulv@ki.au.dk.
authors.forename: Poul F
authors.initials: PF
authors.lastname: Vestergaard
authors.affiliation: The Medical Research LaboratoriesDepartment of Endocrinology and Internal Medicine, Faculty of Health Sciences, Institute of Clinical Medicine, Aarhus University Hospital, Aarhus University, Nørrebrogade 44, DK-8000 Aarhus C, DenmarkDepartment of Growth and ReproductionUniversity Hospital of Copenhagen, Rigshospitalet, Blegdamsvej 9, 2100 Copenhagen Ø, DenmarkDepartment of Clinical MedicineMR Research Centre Aarhus University Hospital, Skejby, Brendstrupgaardsvej 100, DK-8200 Aarhus N, Denmark.
authors.forename: Mikkel H
authors.initials: MH
authors.lastname: Vendelbo
authors.affiliation: The Medical Research LaboratoriesDepartment of Endocrinology and Internal Medicine, Faculty of Health Sciences, Institute of Clinical Medicine, Aarhus University Hospital, Aarhus University, Nørrebrogade 44, DK-8000 Aarhus C, DenmarkDepartment of Growth and ReproductionUniversity Hospital of Copenhagen, Rigshospitalet, Blegdamsvej 9, 2100 Copenhagen Ø, DenmarkDepartment of Clinical MedicineMR Research Centre Aarhus University Hospital, Skejby, Brendstrupgaardsvej 100, DK-8200 Aarhus N, Denmark.
authors.forename: Steen B
authors.initials: SB
authors.lastname: Pedersen
authors.affiliation: The Medical Research LaboratoriesDepartment of Endocrinology and Internal Medicine, Faculty of Health Sciences, Institute of Clinical Medicine, Aarhus University Hospital, Aarhus University, Nørrebrogade 44, DK-8000 Aarhus C, DenmarkDepartment of Growth and ReproductionUniversity Hospital of Copenhagen, Rigshospitalet, Blegdamsvej 9, 2100 Copenhagen Ø, DenmarkDepartment of Clinical MedicineMR Research Centre Aarhus University Hospital, Skejby, Brendstrupgaardsvej 100, DK-8200 Aarhus N, Denmark.
authors.forename: Anders
authors.initials: A
authors.lastname: Juul
authors.affiliation: The Medical Research LaboratoriesDepartment of Endocrinology and Internal Medicine, Faculty of Health Sciences, Institute of Clinical Medicine, Aarhus University Hospital, Aarhus University, Nørrebrogade 44, DK-8000 Aarhus C, DenmarkDepartment of Growth and ReproductionUniversity Hospital of Copenhagen, Rigshospitalet, Blegdamsvej 9, 2100 Copenhagen Ø, DenmarkDepartment of Clinical MedicineMR Research Centre Aarhus University Hospital, Skejby, Brendstrupgaardsvej 100, DK-8200 Aarhus N, Denmark.
authors.forename: Steffen
authors.initials: S
authors.lastname: Ringgard
authors.affiliation: The Medical Research LaboratoriesDepartment of Endocrinology and Internal Medicine, Faculty of Health Sciences, Institute of Clinical Medicine, Aarhus University Hospital, Aarhus University, Nørrebrogade 44, DK-8000 Aarhus C, DenmarkDepartment of Growth and ReproductionUniversity Hospital of Copenhagen, Rigshospitalet, Blegdamsvej 9, 2100 Copenhagen Ø, DenmarkDepartment of Clinical MedicineMR Research Centre Aarhus University Hospital, Skejby, Brendstrupgaardsvej 100, DK-8200 Aarhus N, Denmark.
authors.forename: Niels
authors.initials: N
authors.lastname: Møller
authors.affiliation: The Medical Research LaboratoriesDepartment of Endocrinology and Internal Medicine, Faculty of Health Sciences, Institute of Clinical Medicine, Aarhus University Hospital, Aarhus University, Nørrebrogade 44, DK-8000 Aarhus C, DenmarkDepartment of Growth and ReproductionUniversity Hospital of Copenhagen, Rigshospitalet, Blegdamsvej 9, 2100 Copenhagen Ø, DenmarkDepartment of Clinical MedicineMR Research Centre Aarhus University Hospital, Skejby, Brendstrupgaardsvej 100, DK-8200 Aarhus N, Denmark.
authors.forename: Niels
authors.initials: N
authors.lastname: Jessen
authors.affiliation: The Medical Research LaboratoriesDepartment of Endocrinology and Internal Medicine, Faculty of Health Sciences, Institute of Clinical Medicine, Aarhus University Hospital, Aarhus University, Nørrebrogade 44, DK-8000 Aarhus C, DenmarkDepartment of Growth and ReproductionUniversity Hospital of Copenhagen, Rigshospitalet, Blegdamsvej 9, 2100 Copenhagen Ø, DenmarkDepartment of Clinical MedicineMR Research Centre Aarhus University Hospital, Skejby, Brendstrupgaardsvej 100, DK-8200 Aarhus N, Denmark.
authors.forename: Jens O L
authors.initials: JO
authors.lastname: Jørgensen
mesh_terms: D000273:Adipose Tissue / Q000187:drug effects / Q000378:metabolism*; D000328:Adult; D000367:Age Factors; D000368:Aged; D000369:Aged, 80 and over; D005260:Female; D019382:Human Growth Hormone / Q000378:metabolism* / Q000494:pharmacology; D006801:Humans; D008297:Male; D008875:Middle Aged; D018482:Muscle, Skeletal / Q000187:drug effects / Q000378:metabolism*; D012737:Sex Factors; D015398:Signal Transduction / Q000187:drug effects / Q000235:genetics; D055815:Young Adult
chemical_list: D019382:Human Growth Hormone