Estrogen-Mediated Regulation of p38 Mitogen-Activated Protein Kinase in Human Endometrium

Seval, Yasemin; Çakmak, Hakan; Kayisli, Umit A.; Arıcı, Aydın

doi:10.1210/jc.2005-2132

Cited by 75 publications

(67 citation statements)

References 49 publications

(35 reference statements)

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“…The presence of VEGF mRNA and protein has been demonstrated in the human and mammalian endometrium throughout the menstrual cycle, with an increase in the late proliferative and luteal phases [38,41,46]. A previous study suggested that endometrial proliferation was stimulated by estrogen, while endometrial angiogenesis was stimulated by progesterone, with estrogen acting as a cell mitogen and progesterone, in contrast, acting as a differentiation factor [47]. In the present study, VEGF protein was observed in luminal epithelial cells and glandular cells in early pregnancy, whereas VEGFR1 and VEGFR2 were detected in stromal cells of the endometrium.…”

Section: Discussionmentioning

confidence: 99%

Seasonal Changes in Immunoreactivity of Vascular Endothelial Factor and its Receptors VEGFR1 and VEGFR2 in the Uterus of Wild Ground Squirrels (<i>Citellus dauricus</i> Brandt)

Weng

Sheng

et al. 2012

Journal of Reproduction and Development

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Abstract. In this study, we investigated the immunoreactivity of vascular endothelial growth factor (VEGF) and its receptors flt-1 (VEGFR1) and the kinase domain receptor (KDR/Flk-1, VEGFR2) in the uteri of the wild ground squirrels during the estrous period, early pregnancy and nonbreeding period. Cellular localizations of VEGF, VEGFR1 and VEGFR2 were detected by immunohistochemistry, and total proteins were extracted from uterine tissue in the estrous period, early pregnancy and nonbreeding period for Western blotting analysis. In addition, plasma estradiol-17β and progesterone concentrations were measured by radioimmunoassay. Stronger positive staining of VEGF was found in luminal epithelial cells and glandular cells, and its receptors (VEGFR1 and VEGFR2) were observed in stromal cells in the estrous period and early pregnancy compared with the nonbreeding period. The protein levels of VEGF, VEGFR1 and VEGFR2 were significantly higher in the estrous period and early pregnancy as compared with the nonbreeding period. Besides, plasma estradiol-17β and progesterone concentrations were higher in the estrous period and early pregnancy than in the nonbreeding period, suggesting that the immunoreactivities of VEGF, VEGFR1 and VEGFR2 were correlated with changes in plasma estradiol-17β and progesterone concentrations. These results suggested that VEGF and its receptors may be involved in the regulation of seasonal changes in the uterine functions of wild female ground squirrels. Key words: Uterus, VEGF, VEGFR1, VEGFR2, Wild ground squirrel (J. Reprod. Dev. 58: [537][538][539][540][541][542][543] 2012) D uring the reproductive cycle, the uterine endometrium undergoes a precisely timed complex sequence of physiological and morphological changes in preparation for implantation. These changes are controlled primarily by the ovarian steroid hormones 17β-estradiol (E 2 ) and progesterone [1]. During pregnancy, blood flow to the uterus is increased dramatically to meet the rising demands of the growing fetus. Endocrine control of this phenomenon is complex but includes in part the action of many growth factors [2,3]. Vascular endothelial growth factor (VEGF) is a protein with angiogenic activity and a potent stimulator of microvascular permeability [4,5]. It plays an important role in physiological and pathological neovascularization via its receptors Flt1/VEGFR1 and kinase insert domain containing region (KDR)/VEGFR2, both of which have tyrosine kinase activity [6]. In reproductive organs, VEGF is required for normal ovarian angiogenesis and endometrial growth throughout the ovulatory cycle in humans [7,8] and rodents [9,10]. The expression of VEGF and its receptors has been demonstrated in the endometrium in humans and in experimental and domestic animals throughout the menstrual cycle, with an upregulation in the late proliferative and luteal phases [11][12][13][14][15], periods that correspond to angiogenesis and an increase in vascular permeability [16]. However, the expression of VEGF and its receptors VEGFR1 and V...

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Section: Discussionmentioning

confidence: 99%

Seasonal Changes in Immunoreactivity of Vascular Endothelial Factor and its Receptors VEGFR1 and VEGFR2 in the Uterus of Wild Ground Squirrels (<i>Citellus dauricus</i> Brandt)

Weng

Sheng

et al. 2012

Journal of Reproduction and Development

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“…A recent study indicated that E2 induced activation of p38 via non-genomic action [40]. However, there is little information available concerning the non-genomic effect of EDCs on ovarian cancer cells, and the issue of whether EDCs exert a non-genomic effect in ovarian cancer cells remains obscure.…”

Section: Discussionmentioning

confidence: 99%

Cell Growth of Ovarian Cancer Cells is Stimulated by Xenoestrogens through an Estrogen-Dependent Pathway, but Their Stimulation of Cell Growth Appears not to be Involved in the Activation of the Mitogen-Activated Protein Kinases ERK-1 and p38

Park

Kim

et al. 2009

Journal of Reproduction and Development

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Abstract. Although endocrine disrupting chemicals (EDCs) may interfere with the endocrine system(s) of our body and have estrogenicity or androgenicity, the exact mechanism(s) underlying their detrimental effects is not clearly understood. Thus, in this study, we evaluated the effects of EDCs on proliferation and regulation of transcription of estrogen receptor (ER)-positive BG-1 ovarian cancer cells, and their possible mechanisms were further examined. Treatment with bisphenol A (BPA), nonylphenol (NP), octylphenol (OP) and methoxychlor (MXC) for 24 h resulted in an increase of cell proliferation. Treatment with BPA, NP, OP and MXC increased the estrogen response element (ERE) activity. The increase of cell proliferation and activation of ERE were reversed in the presence of an estrogen receptor antagonist, ICI 182780. These results suggest that ER is involved in EDC-mediated pathway in ovarian cancer cells. Based on this, we further investigated the involvement of EDCs in activation of mitogen-activated protein kinase (MAPK) in relation to cell growth. BPA rapidly induced activation of extracellular signal-regulated kinase (ERK) 1/2 and p38 MAPK at 15 min, but the effect of BPA (10 μM) on stimulation of cell growth was not blocked by pretreatment with inhibitors of MEK (PD98059) or p38 (SB203580) in a dose-dependent manner. Taken together, EDC-induced proliferation is mediated by a genomic effect through ERs and ERE, but EDC-activated MAPK is unlikely to be involved in EDC-induced cell growth in estrogen-responsive ovarian cancer cells. Key words: Endocrine disrupting chemical, Estrogen receptor, Estrogen response element, Extracellular signalregulated kinase, Mitogen-activated protein kinase (J. Reprod. Dev. 55: [23][24][25][26][27][28][29] 2009) varian carcinoma is one of the most frequent gynaecologic cancers, following breast, lung and colorectal cancer [1]. Although the biological causes of ovarian cancer remain unknown, hormonal factors such as estrogen or gonadotropins have been implicated in the etiology of ovarian cancer [2]. In addition, it has been reported that endocrine disrupting chemicals (EDCs) may increase the risk of cancer incidence [3,4]. However, the data associated with the effect of EDCs on ovarian cancer cells are scarce.Since EDCs are known as environmental chemicals that interfere with the hormonal balance of vertebrates and invertebrates, they are considered to be important in physiology and the endocrine system [5,6]. EDCs are released from industrial products such as plastics, pesticides, detergents and other synthetic products. It has been proposed that EDCs may increase human health risks and have potentials to affect the immune system and development of vital organs [7][8][9].Bisphenol-A (BPA), alkylphenols, dichloro-diphenyl-trichloroethane (DDT), polychlorinated biphenyls (PCBs) and phthalates are mainly highlighted among EDCs. BPA, a compound used in polycarbonate and epoxy resins, has been implicated as a potent risk factor for women's health [10]. BPA has been widely use...

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“…Another study mentioned that the genistein at dose 45 µM can increase the activity of p38 from the 15th minute until 120th [16]. Several studies support statement that p38 can activate estrogen receptors in endometrial cells [23,24].…”

Section: Intensity Of Intracellular Phospho-p38mentioning

confidence: 89%

Genistein Increase Intracellular Distribution of the High Motility Group Box-1 through p38 Pathway in HeLa culture cells induced by Tumor Necrosis Factor-α

Herbani¹,

Widodo²,

Suyuti³

2014

JTLS

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Cervical cancer is one kind of many cancers that cause death to women around the world. Many studies had support the statement that inflammation has a strong linkage with cancer development. Several factors like proinflammatory factor can influence tumor cell microenvironment, and induce a faster proliferation. TNF-α is suspected can induce proliferation. While cancer itself can induce inflammation, which is marked by several marker. One of them is HMGB1, released from the cell as active secretory lysosomes or passive diffusion. Genistein has demonstrated growth inhibitory effects of various types of cancer cells. It inhibits tyrosine kinase pathway, which can be activated by TNF -α. One of those pathways that have the link with proliferation is p38. This study tries to reveal about inhibitory effect of genistein toward p38 pathway that had been activated by TNF-α. This research was conducted by exposing cultured HeLa cells with various doses of genistein for 90 minutes, and then exposed to TNF-α 10 ng / mL for 20 minutes. Observations were made with a confocal microscope, by staining the cells with pp38-TRITC and HMGB1 antibody. The intensity was measured and analyzed by Fluoview software. The results suggest that there be significant differences between pp38 intranuclear intensity and HMGB1 extranuclear intensity of each dose of genistein (p = 0.000, ANOVA). pp38 and HMGB1 intensity were increased along with increasing genistein dose, but at high dose there were noted decreasing of pp38 and HMGB1 intensity. At apoptotic dose, pp38 and HMGB1 intensity w ere increased markedly, showing the effect of apoptosis. In general, increasing doses of genistein increase intranuclear p38 activation and HMGB1 extranuclear translocation. So there were a strong linkage between p38 activation and HMGB1 translocation in this study.

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Estrogen-Mediated Regulation of p38 Mitogen-Activated Protein Kinase in Human Endometrium

Cited by 75 publications

References 49 publications

Seasonal Changes in Immunoreactivity of Vascular Endothelial Factor and its Receptors VEGFR1 and VEGFR2 in the Uterus of Wild Ground Squirrels (<i>Citellus dauricus</i> Brandt)

Seasonal Changes in Immunoreactivity of Vascular Endothelial Factor and its Receptors VEGFR1 and VEGFR2 in the Uterus of Wild Ground Squirrels (<i>Citellus dauricus</i> Brandt)

Cell Growth of Ovarian Cancer Cells is Stimulated by Xenoestrogens through an Estrogen-Dependent Pathway, but Their Stimulation of Cell Growth Appears not to be Involved in the Activation of the Mitogen-Activated Protein Kinases ERK-1 and p38

Genistein Increase Intracellular Distribution of the High Motility Group Box-1 through p38 Pathway in HeLa culture cells induced by Tumor Necrosis Factor-α

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