Molecular and Cellular Biology Graduate Program, 435 Morrill I North, University of Massachusetts Amherst, 637 North Pleasant Street, Amherst, MA 01003-9298, United States.
Mol Cell Endocrinol. 2011 Feb 20;333(2):151-9. doi: 10.1016/j.mce.2010.12.027. Epub 2010 Dec 25.
Arylhydrocarbon receptor (Ahr) activation by 2,3,7,8-tetrachlordibenzo-p-dioxin (TCDD) interferes with female reproductive functions, but there is little information on the specific targets of TCDD in the hypothalamic-pituitary-gonadal (HPG) axis. In these studies, we found that TCDD upregulated known AhR target genes, cytochrome p450 1a1 (Cyp1a1), Cyp1a2 and Cyp1b1 in the rat pituitary gland. Moreover, 75% of pituitary lactotropes and 45% of gonadotropes contained Ahr mRNA, and most Ahr-containing cells were estrogen receptor 1 (Esr1)-positive. TCDD abrogated estradiol (E(2))-induced prolactin (Prl) expression in vivo and in vitro; conversely, E(2) blocked TCDD upregulation of luteinizing hormone beta (Lhb) and glycoprotein hormone alpha polypeptide (Cga) expression. TCDD had no effect on levels of Ahr mRNA, but upregulated Esr1 mRNA. E(2) independently repressed Ahr and Esr1 expression and blocked TCDD upregulation of Esr1. Thus, complex interactions between Ahr and Esr alter Prl and luteinizing hormone (LH) synthesis by direct actions in lactotropes and gonadotropes. These findings provide important insights into how TCDD disrupts female reproductive functions.
芳香烃受体 (Ahr) 被 2,3,7,8-四氯二苯并对二恶英 (TCDD) 激活会干扰女性生殖功能，但关于 TCDD 在下丘脑-垂体-性腺 (HPG) 轴中的特定靶点知之甚少。在这些研究中，我们发现 TCDD 上调了大鼠垂体中的已知 Ahr 靶基因，细胞色素 p450 1a1 (Cyp1a1)、Cyp1a2 和 Cyp1b1。此外，75%的垂体泌乳素细胞和 45%的促性腺激素细胞含有 Ahr mRNA，并且大多数含有 Ahr 的细胞为雌激素受体 1 (Esr1) 阳性。TCDD 可阻断体内和体外雌二醇 (E(2)) 诱导的催乳素 (Prl) 表达；相反，E(2) 可阻断 TCDD 对促黄体生成素 β (Lhb) 和糖蛋白激素 α 多肽 (Cga) 表达的上调。TCDD 对 Ahr mRNA 水平没有影响，但上调了 Esr1 mRNA。E(2) 可独立抑制 Ahr 和 Esr1 的表达，并阻断 TCDD 对 Esr1 的上调。因此，Ahr 和 Esr 之间的复杂相互作用通过对泌乳素细胞和促性腺激素细胞的直接作用，改变了 Prl 和促黄体生成素 (LH) 的合成。这些发现为 TCDD 如何破坏女性生殖功能提供了重要的见解。
