title: Serum sex steroids and steroidogenesis-related enzyme expression in skeletal muscle during experimental weight gain in men.
abstract: OBJECTIVE
  Low-circulating testosterone is associated with development of type 2 diabetes in obese men. In this study, we examined the effects of experimental overfeeding and weight gain on serum levels of sex hormones and skeletal muscle expression of steroidogenic enzymes in healthy men with (FH+) and without (FH-) a family history of type 2 diabetes.
  
  
  METHODS
  Following a 3-day lead in energy balanced diet, FH+ (n = 9) and FH- men (n = 11) were overfed by 5200 kJ/day (45% fat) for 28 days. Body weight, fasting glucose, insulin, sex steroid, sex hormone binding globulin (SHBG) levels, insulin sensitivity (hyperinsulinaemic-euglycaemic clamp) and body fat (DXA) were assessed in all individuals at baseline and day 28, and sex steroidogenesis-related enzyme expression in vastus lateralis biopsies was examined in a subset (n = 11).
  
  
  RESULTS
  Body weight, fat mass and fasting insulin levels were increased by overfeeding (P < 0.01) and insulin was increased significantly more in FH+ men (P<0.01). Serum sex hormone binding globulin (SHBG) and 5α-dihydrotestosterone (DHT) were reduced with overfeeding (P < 0.05), and serum testosterone and DHT were reduced to a greater extent in FH+ men (P < 0.05). Overfeeding reduced mRNA expression of 3β-hydroxysteroid dehydrogenase (HSD) and 17βHSD (P ≤ 0.007), independently of group. 5α-Reductase (SRD5A1) mRNA expression was not changed overall, but a time by group interaction was observed (P = 0.04).
  
  
  CONCLUSIONS
  Overfeeding reduced SHBG and muscle expression of enzymes involved in the formation of testosterone in skeletal muscle. Men with a family history of T2DM were more susceptible to deleterious outcomes of overfeeding with greater reductions in serum testosterone and DHT and greater increases in markers of insulin resistance, which may contribute to increased risk of developing type 2 diabetes.
authors.affiliation: Ritsumeikan University, Faculty of Sport and Health Science, Kusatsu, Shiga, Japan.
authors.forename: K
authors.initials: K
authors.lastname: Sato
authors.affiliation: Garvan Institute of Medical Research, Darlinghurst, NSW 2010, Australia.
authors.forename: D
authors.initials: D
authors.lastname: Samocha-Bonet
authors.affiliation: ANZAC Research Institute, University of Sydney, Sydney, NSW 2139, Australia.
authors.forename: D J
authors.initials: DJ
authors.lastname: Handelsman
authors.affiliation: Ritsumeikan University, Faculty of Sport and Health Science, Kusatsu, Shiga, Japan.
authors.forename: S
authors.initials: S
authors.lastname: Fujita
authors.affiliation: Discipline of Medicine, The University of Adelaide, Adelaide 5005, Australia.
authors.forename: G A
authors.initials: GA
authors.lastname: Wittert
authors.affiliation: Discipline of Medicine, The University of Adelaide, Adelaide 5005, Australia; Robinson Research Institute, School of Paediatrics and Reproductive Health, The University of Adelaide, Adelaide, South Australia 5005, Australia. Electronic address: leonie.heilbronn@adelaide.edu.au.
authors.forename: L K
authors.initials: LK
authors.lastname: Heilbronn
mesh_terms: D000273:Adipose Tissue / Q000378:metabolism; D001835:Body Weight / Q000502:physiology; D003924:Diabetes Mellitus, Type 2; D004032:Diet; D006801:Humans; D006963:Hyperphagia / Q000097:blood*; D008297:Male; D013256:Steroids / Q000097:blood*; D013739:Testosterone / Q000097:blood* / Q000378:metabolism; D015430:Weight Gain / Q000502:physiology*
chemical_list: D013256:Steroids; D013739:Testosterone
keywords: Insulin resistance; Overfeeding, Serum testosterone; Steroidogenic enzymes