Genomic and non-genomic effects of estrogens on endothelial cells*1

Simoncini, Tommaso; Mannella, Paolo; Fornari, Letizia; Caruso, A.; Varone, G.L.; Genazzani, Andrea Riccardo

doi:10.1016/j.steroids.2004.05.009

Cited by 150 publications

(107 citation statements)

References 46 publications

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“…In immune cells (KarpuzogluSahin et al, 2001;Grimaldi et al, 2005), smooth muscle cells (Rossi et al, 2002;Hertelendy and Zakar, 2004), and endothelial cells, estrogen can rapidly alter the availability of second messengers (Zhu and Smart, 2003;Simoncini et al, 2004). Stimulation of the second messenger system may result in activation of transcription factors such as CREB.…”

Section: Discussionmentioning

confidence: 99%

Estrogen Induces Estrogen Receptor α-Dependent cAMP Response Element-Binding Protein Phosphorylation via Mitogen Activated Protein Kinase Pathway in Basal Forebrain Cholinergic NeuronsIn Vivo

Szegő¹,

Barabás²,

Balog³

et al. 2006

J. Neurosci.

113

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In addition to classical genomic mechanisms, estrogen also exerts nonclassical effects via a signal transduction system on neurons. To study whether estrogen has a nonclassical effect on basal forebrain cholinergic system, we measured the intensity of cAMP response element-binding protein (CREB) phosphorylation (pCREB) in cholinergic neurons after administration of 17␤-estradiol to ovariectomized (OVX) mice. A significant time-dependent increase in the number of pCREB-positive cholinergic cells was detected after estrogen administration in the medial septum-diagonal band (MS-DB) and the substantia innominata (SI). The increase was first observed 15 min after estrogen administration. The role of classical estrogen receptors (ERs) was evaluated using ER knock-out mice in vivo. The estrogeninduced CREB phosphorylation in cholinergic neurons was present in ER␤ knock-out mice but completely absent in ER␣ knock-out mice in MS-DB and SI. A series of in vitro studies demonstrated that estrogen acted directly on cholinergic neurons. Selective blockade of the mitogen activated protein kinase (MAPK) pathway in vivo completely prevented estrogen-induced CREB phosphorylation in cholinergic neurons in MS-DB and SI. In contrast, blockade of protein kinase A (PKA) was effective only in SI. Finally, studies in intact female mice revealed levels of CREB phosphorylation within cholinergic neurons that were similar to those of estrogen-treated OVX mice. These observations demonstrate an ER␣-mediated nonclassical effect of estrogen on the cholinergic neurons and that these actions are present under physiological conditions. They also reveal the role of MAPK and PKA-MAPK pathway activation in nonclassical estrogen signaling in the basal forebrain cholinergic neurons in vivo.

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Section: Discussionmentioning

confidence: 99%

Estrogen Induces Estrogen Receptor α-Dependent cAMP Response Element-Binding Protein Phosphorylation via Mitogen Activated Protein Kinase Pathway in Basal Forebrain Cholinergic NeuronsIn Vivo

Szegő¹,

Barabás²,

Balog³

et al. 2006

J. Neurosci.

113

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“…This consequently leads to an increase or decrease in mRNA levels, the production of associated proteins, and finally a physiologic response. Estradiol also acts on the plasma membrane to initiate signaling pathways in the cytoplasm and regulate cellular functions, called the nongenomic pathway (64,65). Evidence accumulated over the past decade describes a cross-talk between ERs and EGFRs (66).…”

Section: Epidermal Growth Factor Receptormentioning

confidence: 99%

Cyclooxygenase-2, Epidermal Growth Factor Receptor, and Aromatase Signaling in Inflammation and Mesothelioma

Nuvoli¹,

Galati²

2013

Molecular Cancer Therapeutics

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Malignant mesothelioma or mesothelioma is a rare form of cancer that develops from transformed cells originating in the mesothelium, the protective lining that covers many of the internal organs of the body. It is directly linked to asbestos exposure, which acts as a carcinogen by initiating the carcinogenic process. Because of their shape, asbestos fibers can cross the membrane barriers inside the body and cause inflammatory and fibrotic reactions. Such reactions are believed to be the mechanism by which asbestos fibers may trigger malignant mesothelioma in the pleural membrane around the lungs. Carcinogens are known to modulate the transcription factors, antiapoptotic proteins, proapoptotic proteins, protein kinases, cell-cycle proteins, cell adhesion molecules, COX-2, and growth factor signaling pathways. This article reviews recent studies regarding some malignant mesothelioma molecular targets not only for cancer prevention but also for cancer therapy.

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“…Even though the 319 bp promoter fragment did not contain a full ERE consensus site, E2 induction was still observed, albeit significantly reduced. This residual regulation by E2 may be through activation of the ERE half-site at -176 -171, or it may be through a mechanism independent of DNA binding (Aronica et al 1994, Tesarik & Mendoza 1995, Le Mellay et al 1997, Simoncini et al 2004. Interestingly, the 0·5 kb region displays higher luciferase activity than the 1·0 kb full-length promoter region.…”

Section: Discussionmentioning

confidence: 99%

Steroid hormone regulation of Clca3 expression in the murine uterus

Ky²,

Lydon³

et al. 2006

Journal of Endocrinology

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Progesterone (P4) and its cognate receptor, the progesterone receptor (PGR), have important roles in the establishment and maintenance of pregnancy in the murine uterus. In previous studies, using high-density DNA microarray analysis, we identified a subset of genes whose expression is repressed by chronic P4-PGR activation in the uterus. The Clca3 gene is one of the genes whose expression is the most significantly downregulated by P4 and PGR. In the present study, we performed real-time RT-PCR and in situ hybridization to investigate the regulation of Clca3 by P4 and determine the pattern of expression of Clca3 in the uterus during early pregnancy. This analysis shows that Clca3 mRNA transcripts were detected in the luminal and glandular epithelium of the pseudopregnant uterus at day 0·5 and that the expression of Clca3 was not detected after day 3·5. P4 represses Clca3 mRNA synthesis in the luminal epithelial and glandular epithelial cells of the uterus in ovariectomized wild-type mice, but not in Pgr knockout (PRKO) mice. Conversely, estrogen (E2) induces Clca3 expression in the luminal epithelium and glandular epithelium, and this induction was repressed by P4 in the murine uterus. Analysis of the promoter region of Clca3 by in silico and transient transfection analysis in HEC-1A cells identified the regulation of Clca3 by estrogen receptor-alpha (ESR1) within the first 528 bp of 5 -flanking region of the Clca3 gene. Our studies identified Clca3 as a novel downregulated gene of PGR that is a direct target of E2 regulation.

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Genomic and non-genomic effects of estrogens on endothelial cells*1

Cited by 150 publications

References 46 publications

Estrogen Induces Estrogen Receptor α-Dependent cAMP Response Element-Binding Protein Phosphorylation via Mitogen Activated Protein Kinase Pathway in Basal Forebrain Cholinergic NeuronsIn Vivo

Estrogen Induces Estrogen Receptor α-Dependent cAMP Response Element-Binding Protein Phosphorylation via Mitogen Activated Protein Kinase Pathway in Basal Forebrain Cholinergic NeuronsIn Vivo

Cyclooxygenase-2, Epidermal Growth Factor Receptor, and Aromatase Signaling in Inflammation and Mesothelioma

Steroid hormone regulation of Clca3 expression in the murine uterus

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