Duncan W E, Glass A R, Wray H L
Department of Medicine, Walter Reed Army Medical Center, Washington, D.C. 20307-5001.
Endocrinology. 1991 Nov;129(5):2318-24. doi: 10.1210/endo-129-5-2318.
We previously identified a receptor protein for 1,25-dihydroxyvitamin D3 in rat liver nuclei. The present studies were undertaken to investigate the ontogenesis of the hepatic nuclear vitamin D receptor (nVDR) and the estrogen regulation of this receptor in the liver, small intestine, and kidneys. The hepatic nVDR was significantly elevated in adult female rats compared to prepubertal female rats, while in male rats, this increase was not observed. Oophorectomized rats contained significantly less hepatic nVDR than did intact female rats. Administration of estradiol to castrated male or oophorectomized rats increased the hepatic nVDR. Further studies demonstrated that the increase in the hepatic nVDR was observed only after 2 weeks of estradiol treatment and was positively correlated with circulating estradiol concentrations. Castration of male rats did not alter the hepatic nVDR compared to intact male rats nor did testosterone administration to castrated male rats for 4 weeks change the hepatic nVDR concentration. Unlike the liver, intact female rats contained significantly less renal nVDR than did kidneys from intact male or castrated male rats. Estradiol administration to oophorectomized rats significantly decreased the renal nVDR. Renal nVDR concentrations correlated inversely with the serum concentration of estradiol. Castration of male rats had no effect on the renal nVDR. Intestinal nVDR concentrations were unaffected by castration of male rats or by treatment of castrated male rats with estrogen for up to 4 weeks. These results indicate that estradiol increases the nVDR in liver, decreases the nVDR in kidney and does not change the nVDR in the intestine. Physiological concentrations of testosterone do not regulate the nVDR in these tissues. Estradiol regulation of this receptor is organ specific and, therefore, conclusions about the regulation of the nVDR in one tissue cannot be extrapolated to other tissues.
我们之前在大鼠肝细胞核中鉴定出一种1,25 - 二羟基维生素D3的受体蛋白。目前的研究旨在探讨肝脏、小肠和肾脏中肝细胞核维生素D受体（nVDR）的个体发生以及该受体的雌激素调节作用。与青春期前雌性大鼠相比，成年雌性大鼠的肝nVDR显著升高，而在雄性大鼠中未观察到这种增加。去卵巢大鼠的肝nVDR含量明显低于完整雌性大鼠。给去势雄性或去卵巢大鼠注射雌二醇可增加肝nVDR。进一步研究表明，仅在雌二醇治疗2周后才观察到肝nVDR增加，且与循环雌二醇浓度呈正相关。与完整雄性大鼠相比，雄性大鼠去势并未改变肝nVDR，给去势雄性大鼠注射睾酮4周也未改变肝nVDR浓度。与肝脏不同，完整雌性大鼠的肾脏nVDR含量明显低于完整雄性或去势雄性大鼠的肾脏。给去卵巢大鼠注射雌二醇可显著降低肾脏nVDR。肾脏nVDR浓度与雌二醇血清浓度呈负相关。雄性大鼠去势对肾脏nVDR无影响。雄性大鼠去势或给去势雄性大鼠注射雌激素长达4周对肠道nVDR浓度均无影响。这些结果表明，雌二醇增加肝脏中的nVDR，降低肾脏中的nVDR，且不改变肠道中的nVDR。睾酮的生理浓度不调节这些组织中的nVDR。雌二醇对该受体的调节具有器官特异性，因此，关于一个组织中nVDR调节的结论不能外推至其他组织。
