Hormonal regulation of hepatitis B virus gene expression: influence of androgen receptor.
Adult HBV-transgenic males produce more hepatitis B surface antigen (HBsAg) in serum than females. The difference decreases with castration and is restored with testosterone replacement. To investigate the contribution of the androgen receptor in this process, HBV-transgenic males were mated with females heterozygous for the testicular feminization mutation (Tfm), an X-linked gene with 90% reduced androgen receptor. A total of 19 phenotypic HBV-transgenic females were studied, of which eight XYTfm females were identified by the presence of Y-chromosome DNA using molecular hybridization. The 11 normal (XX) females had 11.7 +/- 3.5 micrograms/mL (mean +/- SD) of HBsAg in their serum, whereas the Tfm (XY) females had 17.1 +/- 5.9 micrograms/mL (p < 0.05). However, the Tfm (XY) females produced less HBsAg than 33 normal (XY) males (41 +/- 12 micrograms/mL), and the overall ratio of male/female HBsAg levels was reduced: XY/XX = 3 versus XYTfm/XX = 1.5. Although dexamethasone caused an increase in XYTfm and XX mice, testosterone did not increase HBsAg in XYTfm. These data indicate that hepatitis B expression as measured by HBsAg levels in this animal model is mediated through an androgen receptor.
Breidbart
S
S
Department of Pediatrics, Albert Einstein College of Medicine, Bronx, New York.
Burk
R D
RD
Saenger
P
P
D013734:Androgen-Insensitivity Syndrome / Q000150:complications / Q000235:genetics; D000818:Animals; D003907:Dexamethasone / Q000494:pharmacology; D005260:Female; D015967:Gene Expression Regulation, Viral / Q000187:drug effects*; D005838:Genotype; D006509:Hepatitis B / Q000150:complications; D006514:Hepatitis B Surface Antigens / Q000096:biosynthesis* / Q000235:genetics; D006515:Hepatitis B virus / Q000187:drug effects* / Q000235:genetics; D008297:Male; D051379:Mice; D008822:Mice, Transgenic; D009919:Orchiectomy; D010641:Phenotype; D011944:Receptors, Androgen / Q000172:deficiency / Q000187:drug effects / Q000235:genetics / Q000502:physiology*; D013739:Testosterone / Q000494:pharmacology*
D006514:Hepatitis B Surface Antigens; D011944:Receptors, Androgen; D013739:Testosterone; D003907:Dexamethasone