Chatterjee B, Roy A K
Department of Cellular and Structural Biology, University of Texas Health Science Center, San Antonio 78284.
J Steroid Biochem Mol Biol. 1990 Nov 20;37(3):437-45. doi: 10.1016/0960-0760(90)90495-7.
The hepatic tissue of the male rat exhibits a gradual decline and ultimate loss in androgen responsiveness during in vivo aging. Appearance of the age-associated androgen insensitivity can be delayed by dietary calorie restriction, an effective means for life-span extension. The androgen receptor mRNA is detectable in the liver only in its androgen-responsive state. Pubertal appearance of hepatic androgen sensitivity is remarkably correlated with the concomitant appearance of a cytoplasmic androgen binding (CAB) protein. Androgen resistance during senescence is associated with the loss of hepatic CAB activity as well. We are investigating the molecular basis for the temporal modulation of this hormone sensitivity through studies on the differential expression of two androgen-responsive marker genes. These are the androgen-repressible SMP-2, and the androgen-inducible alpha 2u-globulin. Androgen resistance of hepatocytes during aging results in repression of the alpha 2u-globulin gene, and derepression of the SMP-2 gene. The structural organizations for both of these genes have been characterized. The role of nuclear transcription factors (androgen receptor and any other transacting factor(s) which may be involved) in the coordinate regulation of alpha 2u-globulin and SMP-2 during aging and nutritional manipulation is being explored to establish the molecular mechanism of andropause in the liver.
雄性大鼠的肝组织在体内衰老过程中，雄激素反应性逐渐下降并最终丧失。与年龄相关的雄激素不敏感性的出现可通过饮食热量限制来延迟，这是延长寿命的有效方法。雄激素受体mRNA仅在肝脏的雄激素反应状态下才可检测到。青春期肝脏雄激素敏感性的出现与细胞质雄激素结合（CAB）蛋白的同时出现显著相关。衰老过程中的雄激素抵抗也与肝脏CAB活性的丧失有关。我们正在通过研究两个雄激素反应性标记基因的差异表达，来探究这种激素敏感性的时间调节的分子基础。这两个基因是雄激素可抑制的SMP-2和雄激素诱导的α2u球蛋白。衰老过程中肝细胞的雄激素抵抗导致α2u球蛋白基因的抑制和SMP-2基因的去抑制。这两个基因的结构组织均已得到表征。正在探索核转录因子（雄激素受体以及可能涉及的任何其他反式作用因子）在衰老和营养操纵过程中对α2u球蛋白和SMP-2的协同调节中的作用，以确立肝脏雄激素缺乏症的分子机制。
