Dou Q, Zhao Y, Tarnuzzer R W, Rong H, Williams R S, Schultz G S, Chegini N
Department of Obstetrics and Gynecology, University of Florida College of Medicine, Gainesville 32610, USA.
J Clin Endocrinol Metab. 1996 Sep;81(9):3222-30. doi: 10.1210/jcem.81.9.8784073.
The expression and cellular distribution of transforming growth factor-1 (TGF beta 1) through TGF beta 3 and TGF beta type I-III receptor messenger ribonucleic acid (mRNA) and protein were analyzed in leiomyomata from patients receiving GnRH agonist (GnRHa; leuprolide acetate) compared to those in untreated controls. Standard reverse transcription-PCR revealed that the unaffected myometrium and leiomyomata from leuprolide-treated and untreated patients express TGF beta 1-3 and TGF beta type I-III receptor mRNA. The myometrial and leiomyomata smooth muscle cells were the primary site of TGF beta 1-3 and TGF beta type I and II receptor mRNA and protein expression, as determined by in situ hybridization and immunohistochemical localization. These observations indicate that leiomyomata express a higher of level of TGF beta and TGF beta receptor mRNA and protein than unaffected myometrium during the secretory phase of the menstrual cycle, and women who received leuprolide acetate therapy had a substantially lower level of expression than untreated controls. Furthermore, competition-based quantitative reverse transcription-PCR using synthetic internal standards revealed that leiomyomata express a significantly higher number (copies per cell) of TGF beta type II receptor mRNA, followed by TGF beta 1, TGF beta type I receptor, TGF beta 2, and TGF beta 3 (P < 0.05). However, there was a significant decrease in the levels (copies per cell) of TGF beta 1, TGF beta 3, and TGF beta type I and type II receptor mRNA expression in leiomyomata from leuprolide-treated compared to untreated patients (P < 0.05). The data provide further evidence that leiomyomata express mRNA and protein for all components of the TGF beta system, and GnRHa therapy results in down-regulation of their expression. More specifically, these data suggest that TGF beta 1 and TGF beta 3 may play a more important role in leiomyomata growth than TGF beta 2, which leads us to propose that lowering TGF beta and receptor expression may have a direct effect on leiomyomata regression.
分析了接受促性腺激素释放激素激动剂（GnRHa；醋酸亮丙瑞林）治疗的患者的平滑肌瘤中转化生长因子-1（TGFβ1）至TGFβ3以及TGFβⅠ至Ⅲ型受体信使核糖核酸（mRNA）和蛋白的表达及细胞分布，并与未治疗的对照组进行比较。标准逆转录聚合酶链反应显示，醋酸亮丙瑞林治疗组和未治疗组患者的未受影响的子宫肌层和平滑肌瘤均表达TGFβ1至3以及TGFβⅠ至Ⅲ型受体mRNA。通过原位杂交和免疫组化定位确定，子宫肌层和平滑肌瘤的平滑肌细胞是TGFβ1至3以及TGFβⅠ和Ⅱ型受体mRNA和蛋白表达的主要部位。这些观察结果表明，在月经周期的分泌期，平滑肌瘤表达的TGFβ和TGFβ受体mRNA及蛋白水平高于未受影响的子宫肌层，且接受醋酸亮丙瑞林治疗的女性其表达水平明显低于未治疗的对照组。此外，使用合成内标进行的基于竞争的定量逆转录聚合酶链反应显示，平滑肌瘤表达的TGFβⅡ型受体mRNA数量（每细胞拷贝数）显著更高，其次是TGFβ1、TGFβⅠ型受体、TGFβ2和TGFβ3（P<0.05）。然而，与未治疗的患者相比，醋酸亮丙瑞林治疗的患者的平滑肌瘤中TGFβ1、TGFβ3以及TGFβⅠ和Ⅱ型受体mRNA表达水平（每细胞拷贝数）显著降低（P<0.05）。数据进一步证明平滑肌瘤表达TGFβ系统所有成分的mRNA和蛋白，且GnRHa治疗导致其表达下调。更具体地说，这些数据表明TGFβ1和TGFβ3在平滑肌瘤生长中可能比TGFβ2发挥更重要的作用，这使我们提出降低TGFβ和受体表达可能对平滑肌瘤消退有直接影响。
