Increased progesterone receptor expression in uterine leiomyoma: correlation with age, number of leiomyomas, and clinical symptoms

Tsigkou, Anastasia; Reis, Fernando M.; Lee, Meng H; Jiang, Bingjie; Tosti, Claudia; Centini, Gabriele; Shen, Fu‐Ming; Chen, Youguo; Petraglia, Felice

doi:10.1016/j.fertnstert.2015.04.024

Cited by 48 publications

(34 citation statements)

References 33 publications

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“…Here, we have demonstrated that E 2 and P 4 work synergistically on rat MSCs to drive proliferation. It has been suggested that P 4 is a major driver of fibroid cell growth, and the primary role of E 2 is to increase transcription of progesterone receptors (PR) . However, we found that E 2 alone was able to induce a marked increase in myometrial Stro1 + /CD44 + MSCs, which suggests that its function is not merely to induce PR, but to act as a potent mitogen for these cells .…”

Section: Discussioncontrasting

confidence: 62%

Developmental Exposure to Endocrine Disruptors Expands Murine Myometrial Stem Cell Compartment as a Prerequisite to Leiomyoma Tumorigenesis

et al. 2016

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Despite the high prevalence and major negative impact of uterine fibroids (UFs) on women's health, their pathogenesis remains largely unknown. While tumor-initiating cells have been previously isolated from UFs, the cell of origin for these tumors in normal myometrium has not been identified. We isolated cells with Stro1/CD44 surface markers from normal myometrium expressing stem cell markers Oct-4/c-kit/nanog that exhibited the properties of myometrial stem/progenitor-like cells (MSCs). Using a murine model for UFs, we showed that the cervix was a hypoxic "niche" and primary site (96%) for fibroid development in these animals. The pool size of these MSCs also responded to environmental cues, contracting with age and expanding in response to developmental environmental exposures that promote fibroid development. Translating these findings to women, the number of MSCs in unaffected human myometrium correlated with risk for developing UFs. Caucasian (CC) women with fibroids had increased numbers of MSCs relative to CC women without fibroids, and African-American (AA) women at highest risk for these tumors had the highest number of MSCs: AA-with fibroids > CC-with fibroids > AA-without fibroids > CC-without fibroids. These data identify Stro1 /CD44 MSCs as MSC/progenitor cell for UFs, and a target for ethnic and environmental factors that increase UF risk. Stem Cells 2017;35:666-678.

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Section: Discussioncontrasting

confidence: 62%

Developmental Exposure to Endocrine Disruptors Expands Murine Myometrial Stem Cell Compartment as a Prerequisite to Leiomyoma Tumorigenesis

et al. 2016

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“…In UFs, progesterone regulates many targets, which may play an important role in UF pathogenesis (Table 1) (77–79). A direct functional link between progesterone and UF development was shown in a mouse xenograft model, where fibroid tumor growth was associated with administration of estrogen plus progesterone, but not with estrogen administration alone.…”

Section: Pathogenesis Of Uterine Fibroidsmentioning

confidence: 99%

Endocrine-disrupting chemicals and uterine fibroids

Katz

Yang

Treviño

et al. 2016

Fertility and Sterility

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Uterine fibroids are the most frequent gynecologic tumor, affecting 70–80% of women over their lifetime. Although these tumors are benign, they can cause significant morbidity and may require invasive treatments such as myomectomy and hysterectomy. Many risk factors for these tumors have been identified, including environmental exposures to endocrine disrupting chemicals (EDCs), e.g. genestein, diethylstilbestrol etc. Uterine development may be a particularly sensitive window to environmental exposures, as some perinatal EDC exposures have been shown to increase tumorigenesis in both rodent models and human epidemiological studies. While the mechanisms by which EDC exposures may increase tumorigenesis are still being elucidated, epigenetic reprogramming of the developing uterus is an emerging hypothesis. Given the remarkably high incidence of uterine fibroids, and their significant impact on women’s health, understanding more about how prenatal exposures to EDCs (and other environmental agents) may increase fibroid risk could be key to developing prevention and treatment strategies in the future.

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“…Progesterone may play an important role in UF development, stimulating cellular proliferation and fibroid growth . Fibroids express elevated levels of both types of progesterone receptors (PR), PR‐α and PR‐β, compared to the surrounding myometrium . These findings suggest a certain role of progesterone and PR in UF pathogenesis but not in hypertension, progesterone being a mineralocorticoid receptor (MR) antagonist.…”

Section: Introductionmentioning

confidence: 99%

Uterine fibroids and risk of hypertension: Implication of inflammation and a possible role of the renin‐angiotensin‐aldosterone system

Armanini

Sabbadin

Donà

et al. 2018

J of Clinical Hypertension

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| INTRODUC TI ONHaan and colleagues 1 reported a cross-sectional study on the association between uterine fibroids (UF), hypertension, and asymptomatic organ damage. The major question that arises from this study is, Are UF directly linked to hypertension or is hyper- | ANG I OTEN S IN II AND ALDOS TERONE COMMITMENT IN UFA previous study 8 has found a significant association between A1166C polymorphism in the angiotensin II type 1 receptor (AT1R) gene and UF. Angiotensin II and aldosterone are involved in cell proliferation, angiogenesis, inflammation, and fibrosis. Moreover, angiotensin

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Increased progesterone receptor expression in uterine leiomyoma: correlation with age, number of leiomyomas, and clinical symptoms

Cited by 48 publications

References 33 publications

Developmental Exposure to Endocrine Disruptors Expands Murine Myometrial Stem Cell Compartment as a Prerequisite to Leiomyoma Tumorigenesis

Developmental Exposure to Endocrine Disruptors Expands Murine Myometrial Stem Cell Compartment as a Prerequisite to Leiomyoma Tumorigenesis

Endocrine-disrupting chemicals and uterine fibroids

Uterine fibroids and risk of hypertension: Implication of inflammation and a possible role of the renin‐angiotensin‐aldosterone system

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