title: Sex hormone-binding globulin gene expression and insulin resistance.
abstract: BACKGROUND
  The plasma level of sex hormone binding globulin (SHBG), a glycoprotein produced by hepatocytes, is subject to genetic, hormonal, metabolic, and nutritional regulation, and is a marker for the development of the metabolic syndrome and diabetes.
  
  
  OBJECTIVE
  Because the mechanism for these associations is unclear, and no studies of SHBG gene expression in humans have been published, SHBG mRNA was measured in human liver samples and related to anthropometric data.
  
  
  METHODS
  Inpatients at a private, nonprofit, university-associated hospital were studied.
  
  
  METHODS
  Subjects were fifty five adult men and women undergoing hepatic resection as treatment for cancer.
  
  
  METHODS
  Main outcome measures were SHBG mRNA and serum SHBG levels.
  
  
  RESULTS
  SHBG mRNA was a strong predictor of serum SHBG with higher levels of the mRNA and protein in women than in men. The relationship between SHBG mRNA and circulating SHBG differed in males and females consistent with a sex difference in post-transcriptional regulation. A strong positive correlation was found between the level of the mRNA for the transcription factor HNF4α and SHBG mRNA. Insulin resistance (IR), assessed by homeostatis model assessment, was related inversely to SHBG mRNA and to HNF4α mRNA as well as to circulating SHBG levels. These mRNAs, as well as serum SHBG, were higher when the hepatic triglyceride concentration was low, and decreased with increasing body mass index but were unrelated to age.
  
  
  CONCLUSIONS
  Fat accumulation in liver and IR are important determinants of SHBG gene expression and thereby circulating SHBG levels that are perhaps mediated through effects on the transcription factor HNF4α. These findings provide a potential mechanism to explain why low SHBG predicts the development of type 2 diabetes.
authors.affiliation: Division of Endocrinology, Metabolism and Diabetes (S.J.W., J.G., M.K., D.T.G.), Division of Surgical Oncology (C.S.), Clinical Pathology Associates, Norton Healthcare (C.A.W.), and Department of Epidemiology and Population Health (R.B.), University of Louisville, Louisville, Kentucky 40202.
authors.forename: Stephen J
authors.initials: SJ
authors.lastname: Winters
authors.forename: Jyothi
authors.initials: J
authors.lastname: Gogineni
authors.forename: Marjan
authors.initials: M
authors.lastname: Karegar
authors.forename: Charles
authors.initials: C
authors.lastname: Scoggins
authors.forename: Chris A
authors.initials: CA
authors.lastname: Wunderlich
authors.forename: Richard
authors.initials: R
authors.lastname: Baumgartner
authors.forename: Dushan T
authors.initials: DT
authors.lastname: Ghooray
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D003924:Diabetes Mellitus, Type 2 / Q000235:genetics; D005234:Fatty Liver / Q000235:genetics / Q000473:pathology; D005260:Female; D015870:Gene Expression / Q000235:genetics; D051557:Hepatocyte Nuclear Factor 4 / Q000235:genetics / Q000378:metabolism; D006801:Humans; D007333:Insulin Resistance / Q000235:genetics*; D008099:Liver / Q000378:metabolism; D008297:Male; D024821:Metabolic Syndrome / Q000235:genetics; D008875:Middle Aged; D012738:Sex Hormone-Binding Globulin / Q000235:genetics*
chemical_list: C496592:HNF4A protein, human; D051557:Hepatocyte Nuclear Factor 4; D012738:Sex Hormone-Binding Globulin