Expression, menstrual cycle-dependent activation, and bimodal mitogenic effect of transforming growth factor-β1 in human myometrium and leiomyoma

Arıcı, Aydın; Sozen, Ibrahim

doi:10.1067/mob.2003.118

Cited by 56 publications

(57 citation statements)

References 20 publications

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“…TGFb1 is wellknown for its bimodal and dose-dependent effects on the growth of SMCs. Arici and colleagues demonstrated that low concentrations of TGFb1 stimulate cell proliferation in leiomyoma (Arici & Sozen 2003) and vascular cells (Battegay et al 1990), while these stimulatory effects disappear at high TGFb1 concentrations. It has been also shown that increased TGFb1 gene expression induced by angiotensin II led to de novo protein synthesis in cultured vascular SMC (Koibuchi et al 1993).…”

Section: Discussionmentioning

confidence: 99%

The expression of transforming growth factor β in pregnant rat myometrium is hormone and stretch dependent

Shynlova

Tsui²,

Dorogin³

et al. 2007

Reproduction

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From a quiescent state in early pregnancy to a highly contractile state in labor, the myometrium displays tremendous growth and remodeling. We hypothesize that the transforming growth factor b (TGFb) system is involved in the differentiation of pregnant myometrium throughout gestation and labor. Furthermore, we propose that during pregnancy the mechanical and hormonal stimuli play a role in regulating myometrial TGFbs. The expression of TGFb1-3 mRNAs and proteins was examined by real-time PCR, Western immunoblot, and localized with immunohistochemistry in the rat uterus throughout pregnancy and labor. Tgfb1-3 genes were expressed differentially in pregnant myometrium. Tgfb2 gene was not affected by pregnancy, whereas the Tgfb1 gene showed a threefold increase during the second half of gestation. In contrast, we observed a dramatic bimodal change in Tgfb3 gene expression throughout pregnancy. Tgfb3 mRNA levels first transiently increased at mid-gestation (11-fold on day 14) and later at term (45-fold at labor, day 23). Protein expression levels paralleled the changes in mRNA. Treatment of pregnant rats with the progesterone (P4) receptor antagonist RU486 induced premature labor on day 19 and increased Tgfb3 mRNA, whereas artificial maintenance of elevated P4 levels at late gestation (days 20-23) caused a significant decrease in the expression of Tgfb3 gene. In addition, Tgfb3 was up-regulated specifically in the gravid horn of unilaterally pregnant rats subjected to a passive biological stretch imposed by the growing fetuses, but not in the empty horn. Collectively, these data indicate that the TGFb family contributes in the regulation of myometrial activation at term integrating mechanical and endocrine signals for successful labor contraction. Reproduction (2007) 134 503-511

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Section: Discussionmentioning

confidence: 99%

The expression of transforming growth factor β in pregnant rat myometrium is hormone and stretch dependent

Shynlova

Tsui²,

Dorogin³

et al. 2007

Reproduction

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“…Primary cells cultured from myometrium and leiomyoma tissues were successfully used to demonstrate the effect of various hormones on cellular proliferation and regulation (15)(16)(17)(18)(19). They were also used to study the expression of various cytokines, e.g., monocyte chemotactic protein-1 (MCP-1) (20) and transforming growth factor (TGF)-␤ (21)(22)(23)(24)(25). These models are quite powerful, but can suffer from various limitations that can lead one to question the similarity of the tissue culture with the progenitor tissue.…”

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confidence: 99%

Novel method to characterize primary cultures of leiomyoma and myometrium with the use of confirmatory biomarker gene arrays

Malik

Catherino

2007

Fertility and Sterility

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“…TGF-␤ regulates its own expression, the expression of ECM, matrix metalloproteinases (MMP) and tissue inhibitor of MMP, as well as the growth of leiomyoma and myometrial smooth muscle cells [8] . TGF-␤ induced significantly more thymidine incorporation in the leiomyoma cells compared with myometrial cells [21] . In addition, TGF-␤ expression in myometrial cells adjacent to leiomyoma cells was significantly increased.…”

Section: Discussionmentioning

confidence: 98%

Immunohistochemical Characteristics of Intramural Leiomyomata That Enlarge during Controlled Ovarian Hyperstimulation for in vitro Fertilization

Zeyneloglu¹,

Esinler²,

Özdemir

et al. 2008

Gynecol Obstet Invest

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Background/Aims: This study aimed to determine the immunohistochemical characteristics of intramural leiomyomata that enlarged during controlled ovarian hyperstimulation (COH) for in vitro fertilization (IVF). Methods: For thisretrospective case-control clinical study and immunohistochemical analysis, 5 patients with enlarged intramural leiomyomata during COH for IVF, who had undergone myomectomy immediately after a failed IVF cycle, were recruited retrospectively. Fifteen consecutive patients who had had myomectomy for intramural leiomyomata <5 cm, but had never undergone any infertility treatment, served as the control group. Histological examinations and immunohistochemical staining with proliferating cell nuclear antigen (PCNA), transforming growth factor-β (TGF-β) and fibronectin were performed on all specimens taken from the study and control groups. The main outcome measures were defined as histological and immunohistochemical scores. Results: Hematoxylin and eosin as well as PCNA staining showed increased mitotic index, cellularity and proliferation index in these growing leiomyomata (study group). There were neither increased mitoses nor cellularity in the leiomyomata of the control group, while PCNA, TGF-β and fibronectin scores in the study group were significantly higher than those in the control group (p < 0.001). Conclusion(s): This study is the first to report increased TGF-β, PCNA, cellularity and mitosis in leiomyomata enlarging during COH for IVF. Further studies with larger sample size are needed to determine the role of TGF-β, PCNA and fibronectin in the growth of leiomyomata during COH.

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Expression, menstrual cycle-dependent activation, and bimodal mitogenic effect of transforming growth factor-β1 in human myometrium and leiomyoma

Cited by 56 publications

References 20 publications

The expression of transforming growth factor β in pregnant rat myometrium is hormone and stretch dependent

The expression of transforming growth factor β in pregnant rat myometrium is hormone and stretch dependent

Novel method to characterize primary cultures of leiomyoma and myometrium with the use of confirmatory biomarker gene arrays

Immunohistochemical Characteristics of Intramural Leiomyomata That Enlarge during Controlled Ovarian Hyperstimulation for in vitro Fertilization

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