Stimulation of a rat uterine stromal cell line in culture reveals a molecular switch for endocrine-dependent differentiation

Rider, Virginia; Potapova, Tamara; Dai, Guoli; Soares, Michael J.

doi:10.1677/joe.1.05957

Cited by 4 publications

(6 citation statements)

References 52 publications

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“…Decidual prolactin-related protein (dPRP) is a differentiation-specific marker for uterine stromal cells (Rider et al 2005). Sex steroids and the differentiation agents' cholera toxin and IL-11 activate a dPRP reporter gene in these stromal cell lines (Rider et al 2005). The present results show that b-catenin accumulates in differentiating stromal cells suggesting that the hormonal control of Wnt signaling activates target genes that regulate both proliferation and differentiation.…”

Section: Discussionmentioning

confidence: 62%

“…Many Wnt target genes are cell specific and will only be identified by systematic comparisons between stromal and decidual cells. Decidual prolactin-related protein (dPRP) is a differentiation-specific marker for uterine stromal cells (Rider et al 2005). Sex steroids and the differentiation agents' cholera toxin and IL-11 activate a dPRP reporter gene in these stromal cell lines (Rider et al 2005).…”

Section: Discussionmentioning

confidence: 99%

“…Proliferation was measured using the thiazolyl blue tetrazolium bromide (MTT) assay that has been validated previously in our laboratory (Piva et al 1996). Quiescent stromal cells were stimulated to differentiate by adding progesterone (1 mM), estradiol 17-b (10 nM), cholera toxin (10 ng/ml), and interleukin-11 (IL-11, 10 ng/ml) as detailed (Rider et al 2005).…”

Section: Stromal Cell Line Proliferation and Differentiationmentioning

confidence: 99%

“…Since most target genes involved in Wnt signaling are cell specific, it was of interest to investigate if progesterone-dependent activation of Wnt was restricted to those targets controlling cell proliferation. Rat uterine stromal cell lines proliferate in response to sex steroid plus growth factors (Piva et al 1996) and differentiate in response to sex steroids and differentiation agents (Rider et al 2005). To investigate if Wnt signaling was restricted to proliferating cells, the accumulation of b-catenin was compared between stromal cell simulated to proliferate and differentiate in culture to quiescent stromal cells (Fig.…”

Section: Sex Steroids Stimulate Wnt Target Gene Expressionmentioning

confidence: 99%

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Progesterone initiates Wnt-β-catenin signaling but estradiol is required for nuclear activation and synchronous proliferation of rat uterine stromal cells

Rider

Isuzugawa

Twarog

et al. 2006

Journal of Endocrinology

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Progesterone pretreatment of ovariectomized rat uteri increases the number of synchronously proliferating stromal cells in response to estradiol 17-b. To identify the signals involved in stimulating synchronous proliferation, sexually mature ovariectomized rats were injected with progesterone (2 mg) for 3 consecutive days. Estradiol 17-b (0 . 2 mg) was administered to initiate cell cycle entry. Uterine samples were removed at various times after hormone administration and changes in wingless (Wnt) pathway effectors and gene targets were identified by microarray. Progesterone pretreatment decreased glycogen synthase kinase-3b (GSK-3b) and increased expression of T-cell factor/lymphoid enhancer factor (TCF/LEF). GSK-3b protein decreased markedly in the uterine stroma of progesterone-pretreated uteri with the concomitant appearance of b-catenin in these stromal cells. Translocation of b-catenin from the cytosol to the nuclei in progesterone-pretreated stromal cells was stimulated in response to estradiol. b-Catenin binding to TCF/LEF increased (P!0 . 05) in progesteronepretreated uteri in response to estradiol. Progesterone stimulated the expression of the Wnt target gene urokinase plasminogen activator receptor (uPA-R) in the periluminal uterine stromal cells. The expression of uPA-R increased in progesteronepretreated stromal cells in response to estradiol administration. Together, the results indicate that progesterone initiates Wnt signaling in the uterine stroma by down-regulating GSK-3b. However, nuclear translocation of b-catenin and sufficient complex formation with TCF/LEF to activate stromal cell cycle entry requires estradiol. Stimulation of a uterine stromal cell line to proliferate and differentiate resulted in b-catenin accumulation, suggesting that endocrine-dependent Wnt signaling controls proliferation and differentiation (decidualization).

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Section: Discussionmentioning

confidence: 62%

Section: Discussionmentioning

confidence: 99%

Section: Stromal Cell Line Proliferation and Differentiationmentioning

confidence: 99%

Section: Sex Steroids Stimulate Wnt Target Gene Expressionmentioning

confidence: 99%

See 2 more Smart Citations

Progesterone initiates Wnt-β-catenin signaling but estradiol is required for nuclear activation and synchronous proliferation of rat uterine stromal cells

Rider

Isuzugawa

Twarog

et al. 2006

Journal of Endocrinology

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“…UIII cells have been reported to undergo decidual differentiation in response to arachidonic acid that induces desmin and prolactin expression (Tessier-Prigent et al, 1999). UIII cells have also been shown to respond to medium containing low serum and either progesterone (1 mM), estradiol 17-beta (10 nM), cholera toxin (10 ng/ml) or interleukin-11 (10 ng/ml) through an increase in the expression of a luciferase reporter gene driven by the dPRP promoter (Rider et al, 2005). Here we describe serum-induced in vitro decidualization of UIII cells and characterize the changes in gene expression pattern during this process.…”

Section: Introductionmentioning

confidence: 99%

Changes in global gene expression during in vitro decidualization of rat endometrial stromal cells

Vallejo

Maschi

Mestre-Citrinovitz

et al. 2009

Journal Cellular Physiology

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During the preimplantation phase of pregnancy the endometrial stroma differentiates into decidua, a process that implies numerous morphological changes and is an example of physiological transdifferentiation. Here we show that UIII rat endometrial stromal cells cultured in the presence of calf serum acquired morphological features of decidual cells and expressed decidual markers. To identify genes involved in decidualization we compared gene expression patterns of control and decidualized UIII cells using cDNA microarray. We found 322 annotated genes exhibiting significant differences in expression (>3 fold, FDR > 0.005), of which 312 have not been previously related to decidualization. Analysis of overrepresented functions revealed that protein synthesis, gene expression and chromatin architecture and remodeling are the most relevant modified functions during decidualization. Relevant genes are also found in the functional terms differentiation, cell proliferation, signal transduction, and matrix/structural proteins. Several of these new genes involved in decidualization (Csdc2, Trim27, Eef1a1, Bmp1, Wt1, Aes, Gna12, and Men1) are shown to be also regulated in uterine decidua during normal pregnancy. Thus, the UIII cell culture model will allow future mechanistic studies to define the transcriptional network regulating reprogramming of stromal cells into decidual cells.

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Decidual Cells Produce a Heparin-binding Prolactin Family Cytokine with Putative Intrauterine Regulatory Actions

Alam

Konno

Sahgal

et al. 2008

Journal of Biological Chemistry

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Pregnancy in mice and rats is associated with the production of a large family of hormones/cytokines related to prolactin (PRL). The hormones/cytokines are hypothesized to coordinate maternal and fetal adaptations to pregnancy. In this study, PRLlike protein-J (PLP-J, also known as PRL family 3, subfamily c, member 1 (Prl3c1)) is shown to be a product of the uterine decidua and a regulator of postimplantation intrauterine events. PLP-J-specific antibodies and a series of recombinant PLP-J proteins were generated and used to investigate PLP-J expression and as ligands for investigating biological targets. Decidual PLP-J migrates as a 29-kDa protein and localizes to a band of decidual cells surrounding the trophoblast cell layer on gestation day 8.5. PLP-J ligands specifically bound in situ to the surrounding uterine stromal cells and vasculature within the decidua of gestation day 8.5 implantation sites. We then investigated the in vitro actions of PLP-J on uterine stromal cells and endothelial cells. PLP-J specifically interacted with both cell populations. PLP-J promoted uterine stromal cell proliferation and inhibited endothelial cell proliferation. We determined that PLP-J does not interact with PRL receptors. Instead, PLP-J interacts with heparin-containing molecules, including syndecan-1, which is expressed in gestation day 8.5 pregnant uteri, as well as in uterine stromal cells and endothelial cells. The restricted expression of PLP-J and its specific interactions with uterine stromal cells and endothelial cells suggests that it acts locally and regulates decidual cell development and the endometrial vasculature.Successful pregnancy requires specialized maternal adaptations. Decidualization is a key uterine adaptation associated with the establishment of pregnancy and is characterized by the differentiation of uterine stromal cells (1-4). Decidual cell differentiation is dependent upon ovarian steroid hormone production, and in rodents, it also requires signals emanating from the preimplantation embryo (1, 5). Once formed, decidual cells establish a protective environment, facilitating the development of the placenta and embryo. They promote the redistribution of specific populations of leukocytes and reorganize the uterine vascular network. Intercellular signals elaborated by decidual cells are key mediators of these uterine adaptive responses. Among the decidual cell ligands are a family of cytokines related to prolactin (PRL). 2PRL is an ancient hormone with its origins as a regulator of vertebrate environmental adaptations (6, 7). Some species possess a single member of the PRL family that can be expressed in an assortment of tissues, including the anterior pituitary and uterus through the utilization of cell-specific promoters (8 -10). Other species have undergone a gene expansion within the PRL locus (11). PRL family gene expansion is particularly robust in mice and rats (12)(13)(14). Gene duplication and natural selection have yielded 2 dozen related genes in each of these species. The PRL family ge...

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Stimulation of a rat uterine stromal cell line in culture reveals a molecular switch for endocrine-dependent differentiation

Cited by 4 publications

References 52 publications

Progesterone initiates Wnt-β-catenin signaling but estradiol is required for nuclear activation and synchronous proliferation of rat uterine stromal cells

Progesterone initiates Wnt-β-catenin signaling but estradiol is required for nuclear activation and synchronous proliferation of rat uterine stromal cells

Changes in global gene expression during in vitro decidualization of rat endometrial stromal cells

Decidual Cells Produce a Heparin-binding Prolactin Family Cytokine with Putative Intrauterine Regulatory Actions

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