title: Up-regulation of hepatic alpha-2-HS-glycoprotein transcription by testosterone via androgen receptor activation.
abstract: OBJECTIVE
  Fetuin-A (alpha-2-HS-glycoprotein, AHSG), a liver borne plasma protein, contributes to the prevention of soft tissue calcification, modulates inflammation, reduces insulin sensitivity and fosters weight gain following high fat diet or ageing. In polycystic ovary syndrome, fetuin-A levels correlate with free androgen levels, an observation pointing to androgen sensitivity of fetuin-A expression. The present study thus explored whether the expression of hepatic fetuin-A is modified by testosterone.
  
  
  METHODS
  HepG2 cells were treated with testosterone and androgen receptor antagonist flutamide, and were silenced with androgen receptor siRNA. To test the in vivo relevance, male mice were subjected to androgen deprivation therapy (ADT) for 7 weeks. AHSG mRNA levels were determined by quantitative RT-PCR and fetuin-A protein abundance by Western blotting.
  
  
  RESULTS
  In HepG2 cells, AHSG mRNA expression and fetuin-A protein abundance were both up-regulated following testosterone treatment. The human alpha- 2-HS-glycoprotein gene harbors putative androgen receptor response elements in the proximal 5 kb promoter sequence relative to TSS. The effect of testosterone on AHSG mRNA levels was abrogated by silencing of the androgen receptor in HepG2 cells. Moreover, treatment of HepG2 cells with the androgen receptor antagonist flutamide in presence of endogenous ligands in the medium significantly down-regulated AHSG mRNA expression and fetuin-A protein abundance. In addition, ADT of male mice was followed by a significant decrease of hepatic Ahsg mRNA expression and fetuin-A protein levels.
  
  
  CONCLUSIONS
  Testosterone participates in the regulation of hepatic fetuin-A expression, an effect mediated, at least partially, by androgen receptor activation.
authors.forename: Jakob
authors.initials: J
authors.lastname: Voelkl
authors.forename: Tatsiana
authors.initials: T
authors.lastname: Pakladok
authors.forename: Yun
authors.initials: Y
authors.lastname: Lin
authors.forename: Robert
authors.initials: R
authors.lastname: Viereck
authors.forename: Aleksandra
authors.initials: A
authors.lastname: Lebedeva
authors.forename: Damaris
authors.initials: D
authors.lastname: Kukuk
authors.forename: Bernd J
authors.initials: BJ
authors.lastname: Pichler
authors.forename: Ioana
authors.initials: I
authors.lastname: Alesutan
authors.forename: Florian
authors.initials: F
authors.lastname: Lang
mesh_terms: D000726:Androgen Antagonists / Q000494:pharmacology; D000818:Animals; D001483:Base Sequence; D015153:Blotting, Western; D005485:Flutamide / Q000494:pharmacology; D056945:Hep G2 Cells; D006801:Humans; D008099:Liver / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D008969:Molecular Sequence Data; D034622:RNA Interference; D011944:Receptors, Androgen / Q000235:genetics* / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013739:Testosterone / Q000494:pharmacology*; D014158:Transcription, Genetic / Q000187:drug effects*; D015854:Up-Regulation / Q000187:drug effects; D060749:alpha-2-HS-Glycoprotein / Q000235:genetics* / Q000378:metabolism
chemical_list: D000726:Androgen Antagonists; D011944:Receptors, Androgen; D060749:alpha-2-HS-Glycoprotein; D013739:Testosterone; D005485:Flutamide