Coordinate regulation by diethylstilbestrol of the platelet-derived growth factor-A (PDGF-A) and -B chains and the PDGF receptor alpha- and beta-subunits in the mouse uterus and vagina: potential mediators of estrogen action.
Coordinate regulation by diethylstilbestrol of the platelet-derived growth factor-A (PDGF-A) and -B chains and the PDGF receptor alpha- and beta-subunits in the mouse uterus and vagina: potential mediators of estrogen action.
复制标题
己烯雌酚对小鼠子宫和阴道中血小板源性生长因子-A (PDGF-A) 和 -B 链以及 PDGF 受体 α 和 β 亚基的协调调节：雌激素作用的潜在介质。
作者：
K. Gray;B. Eitzman;K. Raszmann;T. Steed;A. Geboff;J. Mclachlan;M. Bidwell
雌激素对生殖道的影响涉及细胞增殖、迁移和分化，需要很好地协调。多肽生长因子被认为在许多这些细胞过程中起着至关重要的作用。在目前被证实与雌激素作用相关的生长因子中，有表皮生长因子、转化生长因子-α（TGF α）、转化生长因子-β 1（TGF β 1）、TGF β 2、TGF β 3和胰岛素样生长因子-I（IGF-I）。血小板衍生的生长因子（PDGF）也是有效的促有丝分裂剂，其由两条肽链组成，表示为A和B，其二聚化为同种型（PDGF-AA、-AB和-BB），其在功能特性、分泌行为、受体结合和生理作用方面不同。为了研究PDGF-A和-B链以及PDGF受体亚单位α和β在雌激素作用于小鼠生殖道过程中的作用，通过北方和原位RNA分析以及用合成雌激素己烯雌酚（DES）单次处理未成熟CD-1（17至19日龄）小鼠后的免疫组织化学方法，研究了这些基因表达的时间依赖性变化。我们的研究结果表明雌激素调节小鼠子宫和阴道中PDGF配体和受体的信使RNA（mRNA）和蛋白质的表达。北方和原位RNA分析表明，时间依赖性雌激素诱导的这些基因的mRNA水平在这两个组织在治疗后3小时内。然而，子宫和阴道对DES的反应表现出PDGF配体和受体基因独特的mRNA表达谱，特别是在阴道中PDGF-A和两种受体亚基的转录物的诱导比子宫中更短暂。类固醇特异性研究表明，这些基因的mRNA诱导的主要雌激素特异性调节。通过原位杂交分析细胞特异性RNA表达揭示了雌激素治疗后子宫和阴道上皮中PDGF链和受体亚基的转录物的显著诱导，尽管在基质中也注意到mRNA的表达增强，特别是PDGF受体亚基基因。通过免疫组织化学对PDGF配体和受体蛋白分子进行细胞定位，在对照动物的子宫和阴道中检测到所有这些蛋白的显著免疫染色。DES处理后，子宫PDGF配体和受体蛋白的免疫染色水平在6 h内显著降低，而在阴道中观察到的效果不太明显。（摘要截短至400字）
The effects of estrogen on the reproductive tract involve cell proliferation, migration, and differentiation, which need to be well coordinated. Polypeptide growth factors are believed to play a vital role in a number of these cellular processes. Among the growth factors now documented to be associated with estrogen action are epidermal growth factor, transforming growth factor-alpha (TGF alpha), transforming growth factor-beta 1 (TGF beta 1), TGF beta 2, TGF beta 3, and insulin-like growth factor-I (IGF-I). Platelet-derived growth factors (PDGFs) are also potent mitogens, which consist of two peptide chains, denoted A and B, that dimerize to isoforms (PDGF-AA, -AB, and -BB) which differ in their functional properties, secretory behavior, receptor binding, and physiological effects. To study the role of the PDGF-A and -B chains and the PDGF receptor subunits, alpha and beta, during estrogen action in the mouse reproductive tract, time-dependent changes in the expression of these genes were examined by Northern and in situ RNA analyses and by immunohistochemistry after a single treatment of immature CD-1 (17- to 19-day-old) mice with the synthetic estrogen, diethylstilbestrol (DES). Our results demonstrate estrogen modulation of the expression of messenger RNA (mRNA) and protein for the PDGF ligands and receptors in both the uterus and vagina of the mouse. Northern and in situ RNA analyses demonstrate time-dependent estrogen induction of the mRNA levels for these genes in both tissues within 3 h after treatment. However, distinctive mRNA expression profiles for the PDGF ligand and receptor genes are exhibited by the uterus and vagina in response to DES, especially in that the induction of transcripts for PDGF-A and both receptor subunits is more transient in the vagina than in the uterus. Steroid specificity studies demonstrate predominant estrogen-specific regulation of mRNA induction for these genes. Analysis of cell-specific RNA expression by in situ hybridization reveals prominent induction of transcripts for the PDGF chains and receptor subunits in the uterine and vaginal epithelium after estrogen treatment, although enhanced expression of mRNA is also noted in the stroma, particularly for the PDGF receptor subunit genes. Cellular localization of the PDGF ligand and receptor protein molecules by immunohistochemistry detected significant immunostaining for all of these proteins in both the uterus and vagina of control animals. After DES treatment, the uterus exhibits a significant decrease in the level of PDGF ligand and receptor proteins immunostained within 6 h, whereas less dramatic effects ar observed in the vagina.(ABSTRACT TRUNCATED AT 400 WORDS)