Misiti S, Schomburg L, Yen P M, Chin W W
Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts 02115, USA.
Endocrinology. 1998 May;139(5):2493-500. doi: 10.1210/endo.139.5.5971.
Steroid/thyroid/retinoid receptors are members of the nuclear receptor superfamily and ligand-inducible transcription factors. These receptors modulate transcription of various cellular genes, either positively or negatively, by interacting with specific hormone-response elements located in the target gene promoters. Recent data show that nuclear receptors enhance or inhibit transcription by recruiting an array of coactivator and corepressor proteins to the transcription complex. We examined and compared the expression of four coactivator (steroid receptor coactivator-1 and E1A-associated 300-kDa protein) and corepressor (SMRT and N-CoR) genes in a number of tissues including several endocrine glands and cell lines. We also addressed whether their messenger RNA levels are hormonally regulated by studying the effects of thyroid hormone (T3) and estrogen (E2) treatment in rat pituitary cells (GH3) in vitro and in anterior pituitary in vivo. Our studies show that there are distinct tissue-specific expression patterns of these genes. We show that T3 and E2 regulate the expression of steroid receptor coactivator-1 messenger RNA in the anterior pituitary in addition to a gender-related difference. These tissue variations may have physiological implications for heterogeneity of hormone responses that are observed in normal and malignant tissues.
类固醇/甲状腺/维甲酸受体是核受体超家族和配体诱导型转录因子的成员。这些受体通过与位于靶基因启动子中的特定激素反应元件相互作用，正向或负向调节各种细胞基因的转录。最近的数据表明，核受体通过招募一系列共激活因子和共抑制因子蛋白至转录复合物来增强或抑制转录。我们检测并比较了包括多个内分泌腺和细胞系在内的多种组织中四种共激活因子（类固醇受体共激活因子-1和E1A相关300 kDa蛋白）和共抑制因子（SMRT和N-CoR）基因的表达。我们还通过研究甲状腺激素（T3）和雌激素（E2）体外处理大鼠垂体细胞（GH3）以及体内处理垂体前叶的效果，探讨了它们的信使核糖核酸水平是否受激素调节。我们的研究表明，这些基因存在明显的组织特异性表达模式。我们发现，除了性别相关差异外，T3和E2还调节垂体前叶中类固醇受体共激活因子-1信使核糖核酸的表达。这些组织差异可能对在正常组织和恶性组织中观察到的激素反应异质性具有生理意义。
