Suppression of transforming growth factor-beta (TGF beta) and TGF beta receptor messenger ribonucleic acid and protein expression in leiomyomata in women receiving gonadotropin-releasing hormone agonist therapy

Abstract

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.

Gene Expression Profiling of Leiomyoma and Myometrial Smooth Muscle Cells in Response to Transforming Growth Factor-β

“…We demonstrated that GnRHa therapy markedly down-regulates TGF-␤ and TGF-␤ receptor expression and alters the expression and activation of Smads in leiomyoma as well as LSMC (6,8,9). We have also shown that TGF-␤ expression in LSMC and MSMC is inversely regulated by ovarian steroids compared with their antagonists, ICI-182780, ZK98299, and RU486 (8).…”

Increased expression of platelet-derived growth factor C messenger ribonucleic acid in uterine leiomyomata

“…Although the precise etiology of uterine leiomyomata is still unknown, several growth factors such as transforming growth factor-b (TGF-b), connective tissue growth factor, basic fibroblast growth factor, epidermal growth factor, and PDGF have been reported to be involved in the growth of uterine leiomyomata (12)(13)(14)(15). Although two previous reports showed no differences in the levels of PDGF-A and PDGF-B mRNA expression between leiomyomata and myometrial tissues (16,17), PDGF-C was found to be up-regulated in leiomyoma samples compared with myometrial tissues from only five paired samples in one microarray study (18).…”

Standardized uptake values of uterine leiomyoma with 18F-FDG PET/CT: variation with age, size, degeneration, and contrast enhancement on MRI

“…b Fat-suppression, gadolinium-enhanced T1-weighted MRI shows heterogeneous "strong enhancement". c PET shows moderate 18 F-FDG uptake of this leiomyoma: maximum and average SUVs are 3.90 and 2.85, respectively when obtained during the secretory phase of the menstrual cycle [12]. The TGFβ family increases cell proliferation and extracellular matrix production, both of which might play an important role in leiomyoma behavior.…”