Kumar R C, Thakur M K
Biochemistry & Molecular Biology Laboratory, Department of Zoology, Banaras Hindu University, Varanasi 221005, India.
Neurobiol Aging. 2004 Aug;25(7):925-33. doi: 10.1016/j.neurobiolaging.2003.10.011.
Androgen receptor (AR) is expressed in different tissues including the brain and is under regulation by sex steroid hormones. It mediates the action of androgen which plays a key role in learning, memory, and other brain functions that deteriorate with increasing age. We have correlated the expression of AR mRNA with its promoter methylation and their regulation by testosterone and estradiol in the brain cortex of adult and old male and female mice. Results revealed that (i) AR mRNA expression was significantly higher in male than in female mice. (ii) In both sexes, AR mRNA level was down-regulated by testosterone in adult and old, but up-regulated by estradiol only in adult mice. (iii) Methylation of AR core promoter was increased by testosterone, but decreased by estradiol. These findings show that AR mRNA expression and its core promoter methylation are inversely regulated by testosterone and estradiol in the adult mice brain cortex. Such regulation of AR expression might influence androgen action during aging of the mice brain.
雄激素受体(AR)在包括大脑在内的不同组织中表达,并受性类固醇激素的调控。它介导雄激素的作用,雄激素在学习、记忆以及随着年龄增长而衰退的其他脑功能中起关键作用。我们已经将成年和老年雄性及雌性小鼠大脑皮质中AR mRNA的表达与其启动子甲基化以及睾酮和雌二醇对它们的调控进行了关联研究。结果显示:(i)雄性小鼠中AR mRNA的表达显著高于雌性小鼠。(ii)在两性中,成年和老年小鼠的AR mRNA水平均被睾酮下调,但仅成年小鼠中的AR mRNA水平被雌二醇上调。(iii)AR核心启动子的甲基化被睾酮增加,但被雌二醇降低。这些发现表明,在成年小鼠大脑皮质中,AR mRNA表达及其核心启动子甲基化受睾酮和雌二醇的反向调控。AR表达的这种调控可能会影响小鼠大脑衰老过程中的雄激素作用。