title: Dehydroepiandrosterone replacement therapy in hypoadrenal women: protein anabolism and skeletal muscle function.
abstract: OBJECTIVE
  To determine whether dehydroepiandrosterone (DHEA) replacement therapy in hypoadrenal women improves performance, muscle protein accretion, and mitochondrial functions.
  
  
  METHODS
  Thirty-three hypoadrenal women were enrolled in the study from May 1, 2002, through May 31, 2003. Twenty-eight completed a 12-week, prospective, randomized, placebo-controlled, crossover study with either daily placebo or 50 mg of DHEA with a 2-week washout period and then crossed over to the other treatment. Body composition, physical performance, whole-body and muscle protein metabolism, and mitochondrial functions were determined.
  
  
  RESULTS
  Administration of DHEA significantly increased plasma levels of DHEA sulfate, testosterone, and androstenedione but did not change body composition, muscle strength, peak aerobic capacity, and whole-body protein turnover or synthesis rates of mitochondrial, sarcoplasmic, or mixed muscle proteins. Muscle mitochondrial oxidative enzymes and messenger RNA (mRNA) levels of genes encoding mitochondrial proteins and nuclear transcription factors did not change after DHEA administration. However, mRNA levels of muscle myosin heavy chain 1 (P=.004), which determines muscle fiber type, and those of insulinlike growth factor binding proteins 4 and 5 significantly decreased (P=.02 and P=.03, respectively).
  
  
  CONCLUSIONS
  Three months of DHEA administration increased DHEA sulfate and androgen levels but had no effect on physical performance, body composition, protein metabolism, or muscle mitochondrial biogenesis in hypoadrenal women. However, lowering of mRNA levels of binding proteins of insulinlike growth factor 1 and myosin heavy chain 1 suggests potential effects of longterm treatment with DHEA on muscle fiber type.
authors.affiliation: Endocrine Research Unit, Mayo Clinic, Rochester, MN 55905, USA.
authors.forename: Ketan K
authors.initials: KK
authors.lastname: Dhatariya
authors.forename: Laura J S
authors.initials: LJ
authors.lastname: Greenlund
authors.forename: Maureen L
authors.initials: ML
authors.lastname: Bigelow
authors.forename: Prabin
authors.initials: P
authors.lastname: Thapa
authors.forename: Ann L
authors.initials: AL
authors.lastname: Oberg
authors.forename: G Charles
authors.initials: GC
authors.lastname: Ford
authors.forename: Jill M
authors.initials: JM
authors.lastname: Schimke
authors.forename: K Sreekumaran
authors.initials: KS
authors.lastname: Nair
mesh_terms: D000309:Adrenal Insufficiency / Q000188:drug therapy*; D000735:Androstenedione / Q000097:blood; D001823:Body Composition / Q000187:drug effects; D018592:Cross-Over Studies; D003687:Dehydroepiandrosterone / Q000627:therapeutic use*; D019314:Dehydroepiandrosterone Sulfate / Q000097:blood; D005260:Female; D020249:Hormone Replacement Therapy; D006801:Humans; D008875:Middle Aged; D008931:Mitochondria, Muscle / Q000187:drug effects / Q000502:physiology; D024101:Mitochondrial Proteins / Q000187:drug effects; D018485:Muscle Fibers, Skeletal / Q000187:drug effects; D009124:Muscle Proteins / Q000187:drug effects; D053580:Muscle Strength / Q000187:drug effects; D018482:Muscle, Skeletal / Q000187:drug effects* / Q000503:physiopathology; D018995:Myosin Heavy Chains / Q000187:drug effects; D010088:Oxidoreductases / Q000187:drug effects; D010101:Oxygen Consumption / Q000187:drug effects; D010919:Placebos; D011446:Prospective Studies; D011506:Proteins / Q000187:drug effects* / Q000378:metabolism; D012333:RNA, Messenger / Q000187:drug effects; D012519:Sarcoplasmic Reticulum / Q000187:drug effects; D013002:Somatomedins / Q000187:drug effects; D013739:Testosterone / Q000097:blood; D014157:Transcription Factors / Q000187:drug effects
chemical_list: D024101:Mitochondrial Proteins; D009124:Muscle Proteins; D010919:Placebos; D011506:Proteins; D012333:RNA, Messenger; D013002:Somatomedins; D014157:Transcription Factors; D013739:Testosterone; D000735:Androstenedione; D003687:Dehydroepiandrosterone; D019314:Dehydroepiandrosterone Sulfate; D010088:Oxidoreductases; D018995:Myosin Heavy Chains