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 XY^Tfm1 females were identified by the presence of Y-chromosome DNA using molecular hybridization. The 11 normal (XX) females had 11.7 ± 3.5 µg/mL (mean ± SD) of HBsAg in their serum, whereas the Tfm (XY) females had 17.1 ± 5.9 µg/mL (p < 0.05). However, the Tfm (XY) females produced less HBsAg than 33 normal (XY) males (41 ±12 µg/mL), and the overall ratio of male/female HBsAg levels was reduced: XY/XX = 3 versus XY^Tfm/XX = 1.5. Although dexamethasone caused an increase in XY^Tfm and XX mice, testosterone did not increase HBsAg in XY^Tfm. These data indicate that hepatitis B expression as measured by HBsAg levels in this animal model is mediated through an androgen receptor.