Progesterone down-regulates insulin-like growth factor-I expression in cultured human uterine leiomyoma cells

Yamada, Takashi; Nakago, Satoshi; Kurachi, Osamu; Wang, Jiayin; Takekida, Shigeki; Matsuo, Hiroya; Maruo, Takeshi

doi:10.1093/humrep/deh146

Cited by 47 publications

(30 citation statements)

References 31 publications

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“…The Maruo group in Japan found that progesterone downregulates expression of insulinlike growth factor-I (IGF-1) in human leiomyoma cells (57). They also demonstrated that progesterone upregulates expression of proliferating cell nuclear antigen (PCNA) and epidermal growth factor (EGF), both are known regulators of leiomyoma cellular proliferation (58,59).…”

Section: Progesteronementioning

confidence: 99%

Signaling Pathways in Leiomyoma: Understanding Pathobiology and Implications for Therapy

Borahay

Al-Hendy

Kılıç

et al. 2015

Mol Med

128

147

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Uterine leiomyomas are the most common tumors of the female genital tract, affecting 50% to 70% of females by the age of 50. Despite their prevalence and enormous medical and economic impact, no effective medical treatment is currently available. This is, in part, due to the poor understanding of their underlying pathobiology. Although they are thought to start as a clonal proliferation of a single myometrial smooth muscle cell, these early cytogenetic alterations are considered insufficient for tumor development and additional complex signaling pathway alterations are crucial. These include steroids, growth factors, transforming growth factor-beta (TGF-β)/Smad; wingless-type (Wnt)/β-catenin, retinoic acid, vitamin D, and peroxisome proliferator-activated receptor γ (PPARγ). An important finding is that several of these pathways converge in a summative way. For example, mitogen-activated protein kinase (MAPK) and Akt pathways seem to act as signal integrators, incorporating input from several signaling pathways, including growth factors, estrogen and vitamin D. This underlines the multifactorial origin and complex nature of these tumors. In this review, we aim to dissect these pathways and discuss their interconnections, aberrations and role in leiomyoma pathobiology. We also aim to identify potential targets for development of novel therapeutics.

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Section: Progesteronementioning

confidence: 99%

Signaling Pathways in Leiomyoma: Understanding Pathobiology and Implications for Therapy

Borahay

Al-Hendy

Kılıç

et al. 2015

Mol Med

128

147

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“…There was also a slightly lower neonatal ponderal index in the 400-mg progesterone group (Table 2). Although it is known that progesterone down-regulates insulin-like growth factor 1 (IGF-1) mRNA and protein expression in cultured uterine leiomyoma cells, 23 it seems unlikely that this subtle effect of 400 mg of progesterone on the fetal growth rate of twins could be attributed to a potential IGF-1 down-regulation, because the proportion of neonates with birthweights <2500 g and <1500 g in the 400-mg progesterone group was similar to the other two groups studied.…”

Section: Vaginal Progesterone In Twin Pregnanciesmentioning

confidence: 99%

Increased doses of vaginal progesterone for the prevention of preterm birth in twin pregnancies: a randomised controlled double‐blind multicentre trial

Serra¹,

Perales²,

Meseguer³

et al. 2012

BJOG

100

110

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Objective Previous trials have shown little benefit for preventing preterm birth in twin pregnancies using 90-200 mg of daily vaginal natural progesterone. Higher doses have not been tested. Our aim was to determine the efficacy and safety of two different daily doses of vaginal natural progesterone (200 and 400 mg), compared with placebo, for preventing preterm birth in unselected twin pregnancies.Design Randomised controlled double-blind multicentre trial (1:1:1).Setting The study was carried out in five university centres from Valencia, Murcia and Alicante (Spain).Population Women with dichorionic diamniotic twin pregnancies.Methods The women self-inserted two vaginal pessaries daily, containing placebo (n = 96), 200 mg of natural progesterone (n = 97) or 400 mg of natural progesterone (n = 97), from 20 to 34 weeks of gestation or delivery. Randomisation was performed by an external centre. Data were analysed on an intention-to-treat basis.Main outcome measure Preterm birth rate.Results The baseline characteristics for placebo and progesterone groups were similar. Comparison of the three groups and analysis of progesterone-treated versus untreated women showed similar pregnancy and neonatal outcomes. The proportion of preterm and very preterm births, low birthweight, perinatal mortality and neonatal morbidity showed no differences between the three groups. Similar results were also obtained when comparing the 200-versus 400-mg progesterone groups. No serious adverse effects were encountered.Conclusions Vaginal progesterone therapy was generally well tolerated, but failed to prevent preterm births in unselected dichorionic diamniotic twin pregnancies. The 400-mg progesterone dose offered no advantages over the 200-mg regimen.

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“…Portier et al showed medium with 2% horse serum or Ultroser ® -G to cause muscular differentiation in myoblasts, whereas 10% fetal calf serum does not support differentiation [29]. Using media without any serum could be advantageous for the density of PR [30]. Myoma tissues were cultured in different concentrations in fetal calf serum (FCS), horse serum (HS), Ultroser ® -G (CytoGen), and without any serum or serum replacement.…”

Section: Optimal Serum For Culturing Myoma Tissuementioning

confidence: 99%

Optimized Culture Conditions for Tissue Explants of Uterine Leiomyoma

Fiebitz

Fritsch²,

Reichelt³

et al. 2013

Clin. Lab.

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SUMMARYBackground: Uterine leiomyomas are the most common benign tumours in women, which arise from smooth muscle cells of the uterine myometrium and usually are multicentric. In spite of their frequency pathogenesis is widely unknown, mainly due to the absence of a suitable model system. We describe the systematic optimization of culturing leiomyoma tissue explants in an economical and effective ex vivo system. Methods: Different concentrations of oxygen, different media, sera, hormones, and growth factor supplements were tested. Immunohistochemical stainings with antibodies against hormone receptors as well as specifying proliferation and apoptotic indices and real-time PCR were performed. Results: Main parameters for culturing myoma tissue explants were tested for finding an optimal protocol. Standard medium D-MEM-F12 in combination with the use of horse serum in a reduced concentration of 1% turned out to be optimal for these tissue cultures as well as the addition of estradiol and epidermal growth factor EGF to media. Reduced oxygen content in the incubator air showed no positive effect. Conclusions: For culturing tissue explants of uterine leiomyoma several conditions were optimized. The established tissue culture model allows examining the effects of known and potential therapeutic substances and the influence of immune competent cells in the process of tumour formation to find new targets for medical treatment.

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Progesterone down-regulates insulin-like growth factor-I expression in cultured human uterine leiomyoma cells

Abstract: The present study provided evidence for the first time that progesterone down-regulates IGF-I mRNA and protein expression in cultured leiomyoma cells without affecting IGF-I receptor mRNA expression.

Cited by 47 publications

References 31 publications

Signaling Pathways in Leiomyoma: Understanding Pathobiology and Implications for Therapy

Signaling Pathways in Leiomyoma: Understanding Pathobiology and Implications for Therapy

Increased doses of vaginal progesterone for the prevention of preterm birth in twin pregnancies: a randomised controlled double‐blind multicentre trial

Optimized Culture Conditions for Tissue Explants of Uterine Leiomyoma

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