Francavilla A, Eagon P K, DiLeo A, Van Thiel D H, Panella C, Polimeno L, Amoruso C, Ingrosso M, Aquilino A M, Starzl T E
Gastroenterology. 1986 Jul;91(1):182-8. doi: 10.1016/0016-5085(86)90456-7.
Mammalian liver is a sex steroid-responsive tissue. The effects of these hormones presumably are mediated by hepatic estrogen receptors (ER) and androgen receptors (AR). Serum levels of sex hormones display circadian rhythms. Further, estrogens and androgens are commonly administered; administration of these agents is associated frequently with liver disease. Therefore, we investigated whether the cytosolic and nuclear sex steroid receptors also display a similar circadian rhythm, and whether variations occurred in the distribution of receptors between cytosolic and nuclear compartments. Animals were killed every 4 h from midnight till the following midnight; cytosolic and nuclear levels of both ER and AR were measured. Cytosolic ER reached a maximum level at 4 AM, and a minimum at 8 PM and midnight of both days. Nuclear ER was highest at 8 AM and lowest at 4 PM and 8 PM, a pattern which parallels variations in serum estradiol levels. Cytosolic AR was highest at 8 PM and lowest at midnight and 4 AM. Nuclear AR was highest at 4 AM and lowest at 4 PM and 8 PM. The highest level of nuclear AR does not correspond to the maximum serum testosterone level, which occurred at 4 PM. The total hepatic content of both ER and AR was not constant over the 24-h period, but varied considerably with time of day. These studies suggest that both ER and AR show a distinct circadian rhythm in subcellular compartmentalization, and that total hepatic content of ER and AR varies significantly during a 24-h period.
哺乳动物肝脏是一种对性类固醇有反应的组织。这些激素的作用大概是由肝脏雌激素受体（ER）和雄激素受体（AR）介导的。性激素的血清水平呈现昼夜节律。此外，雌激素和雄激素通常会被使用；使用这些药物常常与肝脏疾病有关。因此，我们研究了胞质和核性类固醇受体是否也呈现类似的昼夜节律，以及受体在胞质和核区室之间的分布是否会发生变化。从午夜到次日午夜，每隔4小时处死一批动物；测量ER和AR的胞质和核水平。胞质ER在凌晨4点达到最高水平，在两天的晚上8点和午夜达到最低水平。核ER在上午8点最高，在下午4点和晚上8点最低，这种模式与血清雌二醇水平的变化相似。胞质AR在晚上8点最高，在午夜和凌晨4点最低。核AR在凌晨4点最高，在下午4点和晚上8点最低。核AR的最高水平与下午4点出现的最高血清睾酮水平并不对应。在24小时内，ER和AR的肝脏总含量并非恒定不变，而是随一天中的时间有很大变化。这些研究表明，ER和AR在亚细胞区室化方面都表现出明显的昼夜节律，并且在24小时内，ER和AR的肝脏总含量有显著变化。
