Haq R, Pfahl M, Chytil F
Department of Biochemistry, Vanderbilt University, Nashville, TN 37232.
Proc Natl Acad Sci U S A. 1991 Sep 15;88(18):8272-6. doi: 10.1073/pnas.88.18.8272.
The multitude of biological effects of the vitamin A metabolite, retinoic acid, are mediated by nuclear retinoic acid receptors (RARs), which are members of the steroid/thyroid hormone receptor superfamily. RAR-alpha, -beta, and -gamma are encoded by three genes from which multiple isoforms can be generated. Recent studies suggest that the expression of at least some RAR isoforms can be regulated by retinoic acid in certain cell lines. Here we examined regulation of RAR expression in the adult animal. RARs were analyzed by Northern blots from lung, liver, and testes of retinol-deficient rats. Retinol deficiency caused a 65-70% decrease in the mRNA levels of lung and liver RAR-beta, whereas no change was observed in RAR-alpha and -gamma mRNA levels in these organs. In the testes of retinol-deficient animals, two transcripts, RAR-alpha 1 (3.7 kb) and RAR-alpha 2 (2.8 kb), were detected as compared with one RAR-alpha 1 (3.7 kb) transcript in retinol-sufficient testes. When retinol-deficient rats were orally administered 1 dose of retinoic acid (100 micrograms per rat), lung RAR-beta mRNA levels started to increase after 1 hr and reached a 16-fold higher level after 4 hr; after 4 hr these retinoic acid-fed rats also showed a 7-fold increase in liver RAR-beta mRNA levels as compared with levels in the retinol-deficient rats. In contrast, liver, lung, and testes RAR-alpha transcripts remained either unchanged or showed only a slight increase in response to retinoic acid. RAR-gamma was constitutively expressed in lung, and its mRNA levels were induced 2-fold by retinoic acid. These results show tissue diversity in the rapid induction of RAR-beta and RAR-gamma by retinoic acid in the adult animal and suggest distinct roles for the various receptor isoforms in the control of the retinoid response.
维生素A代谢产物视黄酸具有多种生物学效应，这些效应由核视黄酸受体（RARs）介导，RARs属于类固醇/甲状腺激素受体超家族成员。RAR-α、-β和-γ由三个基因编码，这些基因可产生多种亚型。最近的研究表明，在某些细胞系中，至少一些RAR亚型的表达可受视黄酸调控。在此，我们研究了成年动物中RAR表达的调控情况。通过Northern印迹法分析了维生素A缺乏大鼠肺、肝和睾丸中的RARs。维生素A缺乏导致肺和肝中RAR-β的mRNA水平下降65%-70%，而这些器官中RAR-α和-γ的mRNA水平未观察到变化。在维生素A缺乏动物的睾丸中，检测到两种转录本，即RAR-α1（3.7 kb）和RAR-α2（2.8 kb），而在维生素A充足的睾丸中仅检测到一种RAR-α1（3.7 kb）转录本。当给维生素A缺乏的大鼠口服一剂视黄酸（每只大鼠100微克）时，肺RAR-β的mRNA水平在1小时后开始升高，4小时后达到高16倍的水平；4小时后，与维生素A缺乏大鼠相比，这些喂食视黄酸的大鼠肝RAR-β的mRNA水平也升高了7倍。相比之下，肝、肺和睾丸中的RAR-α转录本保持不变或对视黄酸仅表现出轻微升高。RAR-γ在肺中组成性表达，其mRNA水平可被视黄酸诱导增加2倍。这些结果表明，成年动物中视黄酸对RAR-β和RAR-γ的快速诱导存在组织多样性，并提示各种受体亚型在类视黄醇反应控制中具有不同作用。
