Department of Biochemistry and Molecular Biology, New York Medical College, Valhalla, New York 10595, USA.
Physiol Behav. 2010 Feb 9;99(2):163-8. doi: 10.1016/j.physbeh.2009.07.011. Epub 2009 Jul 26.
Within the catecholaminergic systems, there are contradictory findings regarding ability of estradiol to regulate expression of genes related to catecholamine biosynthesis. Several parameters important for effects of estradiol on the catecholamine (CA) related enzyme gene expression were examined in two CA regions. Ovariectomized (OVX) female rats were given prolonged estradiol treatments, either in a pulsatile fashion by injections or continuously by pellets. The mode affected the response of tyrosine hydroxylase (TH) and GTP cyclohydrolase I (GTPCH) mRNAs differentially in the nucleus of solitary tract (NTS) and the locus coeruleus (LC). In rostral-medial NTS, TH mRNA levels were increased with injections, but declined in rats administered estradiol by pellets. In LC, a significant change was only observed in GTPCH with injections. These differences may reflect activation of different estrogen receptors (ER). The response to estradiol in the presence of ERalpha and ER beta was examined in PC12 cell culture. Estradiol directly regulated promoter activity of TH, GTPCH and dopamine beta-hydroxylase (DBH) genes. With ERalpha, 17 beta-estradiol elevated TH promoter activity, while there was a decline with ERbeta. In contrast, both DBH and GTPCH promoters were enhanced by 17 beta-estradiol over a wide range of concentrations with either ER subtype. Thus, mode of administration, location examined and ER subtype expressed are important considerations in the overall response of catecholamine related enzymes to estradiol.
在儿茶酚胺能系统中，关于雌二醇调节儿茶酚胺生物合成相关基因表达的能力存在矛盾的发现。在两个儿茶酚胺（CA）相关酶基因区域中，检查了几个对雌二醇对 CA 相关酶基因表达的影响很重要的参数。通过注射或通过植入物连续给予去卵巢（OVX）雌性大鼠延长的雌二醇处理。这种方式影响了孤束核（NTS）和蓝斑核（LC）中酪氨酸羟化酶（TH）和 GTP 环水解酶 I（GTPCH）mRNA 的反应不同。在 NTS 的前内侧，注射增加了 TH mRNA 水平，但在给予雌二醇植入物的大鼠中下降。在 LC 中，仅观察到注射引起的 GTPCH 显著变化。这些差异可能反映了不同雌激素受体（ER）的激活。在 PC12 细胞培养中检查了存在 ERalpha 和 ER beta 时雌二醇的反应。雌二醇直接调节 TH、GTPCH 和多巴胺β-羟化酶（DBH）基因的启动子活性。用 ERalpha，17β-雌二醇升高 TH 启动子活性，而用 ERbeta 则下降。相比之下，在 ER 亚型的广泛浓度范围内，雌二醇均可增强 DBH 和 GTPCH 启动子。因此，给药方式、检查的位置和表达的 ER 亚型是儿茶酚胺相关酶对雌二醇总体反应的重要考虑因素。
