HORMONAL-REGULATION OF HEPATITIS-B VIRUS GENE-EXPRESSION - INFLUENCE OF ANDROGEN RECEPTOR

HORMONAL-REGULATION OF HEPATITIS-B VIRUS GENE-EXPRESSION - INFLUENCE OF ANDROGEN RECEPTOR
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DOI:
10.1203/00006450-199309000-00012
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发表时间:
1993-09-01
期刊:
影响因子:
3.6
通讯作者:
SAENGER, P
SAENGER, P
中科院分区:
医学3区
文献类型:
--
作者:
BREIDBART, S;BURK, RD;SAENGER, P

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成年HBV转基因男性血清中产生的B表面抗原(HBsAg)比女性多。这种差异随着去势而减小,并随着睾酮替代而恢复。为了研究雄激素受体在这一过程中的作用,HBV转基因雄性与睾丸女性化突变(Tfm)杂合子的雌性交配,Tfm是一种雄激素受体减少90%的X连锁基因。共19个表型HBV转基因女性进行了研究,其中8个XY(Tfm)的女性被确定为Y染色体DNA的存在,使用分子杂交。11名正常(XX)女性的血清中HBsAg为11.7 +/- 3.5 mug/mL(平均值+/- SD),而Tfm(XY)女性为17.1 +/- 5.9 gg/mL(p < 0.05)。然而,Tfm(XY)女性产生的HBsAg少于33名正常(XY)男性(41 +/- 12 mug/mL),男性/女性HBsAg水平的总体比值降低:XY/XX = 3 vs XY(Tfm)/XX = 1.5。虽然地塞米松导致XY(Tfm)和XX小鼠的HBsAg增加,但睾酮未增加XY(Tfm)小鼠的HBsAg。这些数据表明,在该动物模型中通过HBsAg水平测量的B型肝炎表达是通过雄激素受体介导的。
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(Tfm) females were identified by the presence of Y-chromosome DNA using molecular hybridization. The 11 normal (XX) females had 11.7 +/- 3.5 mug/mL (mean +/- SD) of HBsAg in their serum, whereas the Tfm (XY) females had 17.1 +/- 5.9 gg/mL (p < 0.05). However, the Tfm (XY) females produced less HBsAg than 33 normal (XY) males (41 +/- 12 mug/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.