Shen E S, Hardenburg J L, Meade E H, Arey B J, Merchenthaler I, López F J
Peptide Pharmacology Section, Women's Health Research Institute, Wyeth-Ayerst Research, Radnor, PA 19087, USA.
Endocrinology. 1999 Jun;140(6):2628-31. doi: 10.1210/endo.140.6.6932.
Estradiol imprinting plays an important role in the regulation of galanin (GAL) gene expression in the rat. In the anterior pituitary gland, GAL gene expression is greatly induced by estrogen. The relative involvement that the two estrogen receptor subtypes, alpha and beta, have in regulating this induction is not known. We have utilized ER alpha-knock-out (ER alphaKO) mice to discriminate the roles of ER alpha and ER beta in the regulation of GAL gene expression in the anterior pituitary gland. Our goals were to measure the effects of estradiol on GAL gene expression by solution hybridization ribonuclease protection assay in wild-type mice and to determine the roles of ER alpha and, indirectly, ER beta by measuring the same response in the ER alphaKO mice. Estradiol treatment for one week elevated GAL gene expression 30-40 fold in the wild-type mouse pituitary. Evaluation of estrogen effects on GAL gene expression in the anterior pituitary of ER alphaKO animals revealed that ER alpha is essential, because no response to estrogen was observed in these animals. Since ER beta mRNA was identified in the anterior pituitary by RT-PCR, but estrogen had no effects on GAL gene expression in the ER alphaKO mice, the beta subtype of ER does not appear to participate in estrogen-evoked GAL gene expression in the mouse anterior pituitary.
雌二醇印记在大鼠甘丙肽(GAL)基因表达的调节中起重要作用。在垂体前叶,雌激素可极大地诱导GAL基因表达。目前尚不清楚雌激素受体α和β这两种亚型在调节这种诱导过程中各自的相对作用。我们利用雌激素受体α基因敲除(ERαKO)小鼠来区分ERα和ERβ在垂体前叶GAL基因表达调节中的作用。我们的目标是通过溶液杂交核糖核酸酶保护试验来测量雌二醇对野生型小鼠GAL基因表达的影响,并通过测量ERαKO小鼠的相同反应来确定ERα以及间接确定ERβ的作用。在野生型小鼠垂体中,雌二醇处理一周可使GAL基因表达提高30至40倍。对ERαKO动物垂体前叶中雌激素对GAL基因表达影响的评估显示,ERα至关重要,因为在这些动物中未观察到对雌激素的反应。由于通过逆转录聚合酶链反应(RT-PCR)在垂体前叶中鉴定出了ERβ信使核糖核酸(mRNA),但雌激素对ERαKO小鼠的GAL基因表达没有影响,因此ER的β亚型似乎不参与小鼠垂体前叶中雌激素诱发的GAL基因表达。