KEGG PATHWAY: map04915

PATHWAY: map04915

Entry

map04915                    Pathway

Name

Estrogen signaling pathway

Description

Estrogens are steroid hormones that regulate a plethora of physiological processes in mammals, including reproduction, cardiovascular protection, bone integrity, cellular homeostasis, and behavior. Estrogen mediates its cellular actions through two signaling pathways classified as "nuclear-initiated steroid signaling" and "membrane-initiated steroid signaling". In the "nuclear" pathway, estrogen binds either ERalpha or ERbeta, which in turn translocates to the nucleus, binds DNA at ERE elements and activates the expression of ERE-dependent genes. In "membrane" pathway, Estrogen can exert its actions through a subpopulation of ER at the plasma membrane (mER) or novel G-protein coupled E2 receptors (GPER). Upon activation of these receptors various signaling pathways (i.e. Ca2+, cAMP, protein kinase cascades) are rapidly activated and ultimately influence downstream transcription factors.

Class

Organismal Systems; Endocrine system

Pathway map

map04915

Estrogen signaling pathway

Other DBs

GO:

0030520

Reference

PMID:16516516

Authors

Zhang D, Trudeau VL

Title

Integration of membrane and nuclear estrogen receptor signaling.

Journal

Comp Biochem Physiol A Mol Integr Physiol 144:306-15 (2006)
DOI:10.1016/j.cbpa.2006.01.025

Reference

PMID:19187465

Authors

Roepke TA, Qiu J, Bosch MA, Ronnekleiv OK, Kelly MJ

Title

Cross-talk between membrane-initiated and nuclear-initiated oestrogen signalling in the hypothalamus.

Journal

J Neuroendocrinol 21:263-70 (2009)
DOI:10.1111/j.1365-2826.2009.01846.x

Reference

PMID:19700741

Authors

McCarthy MM

Title

The two faces of estradiol: effects on the developing brain.

Journal

Neuroscientist 15:599-610 (2009)
DOI:10.1177/1073858409340924

Reference

PMID:18538919

Authors

Kelly MJ, Ronnekleiv OK

Title

Membrane-initiated estrogen signaling in hypothalamic neurons.

Journal

Mol Cell Endocrinol 290:14-23 (2008)
DOI:10.1016/j.mce.2008.04.014

Reference

PMID:16112267

Authors

Kelly MJ, Qiu J, Ronnekleiv OK

Title

Estrogen signaling in the hypothalamus.

Journal

Vitam Horm 71:123-45 (2005)
DOI:10.1016/S0083-6729(05)71005-0

Reference

PMID:18253054

Authors

Raz L, Khan MM, Mahesh VB, Vadlamudi RK, Brann DW

Title

Rapid estrogen signaling in the brain.

Journal

Neurosignals 16:140-53 (2008)
DOI:10.1159/000111559

Reference

PMID:15862823

Authors

Malyala A, Kelly MJ, Ronnekleiv OK

Title

Estrogen modulation of hypothalamic neurons: activation of multiple signaling pathways and gene expression changes.

Journal

Steroids 70:397-406 (2005)
DOI:10.1016/j.steroids.2005.03.004

Reference

PMID:14573532

Authors

Qiu J, Bosch MA, Tobias SC, Grandy DK, Scanlan TS, Ronnekleiv OK, Kelly MJ

Title

Rapid signaling of estrogen in hypothalamic neurons involves a novel G-protein-coupled estrogen receptor that activates protein kinase C.

Journal

J Neurosci 23:9529-40 (2003)
DOI:10.1523/JNEUROSCI.23-29-09529.2003

Reference

PMID:14993035

Authors

Kelly MJ, Qiu J, Ronnekleiv OK

Title

Estrogen modulation of G-protein-coupled receptor activation of potassium channels in the central nervous system.

Journal

Ann N Y Acad Sci 1007:6-16 (2003)
DOI:10.1196/annals.1286.001

Reference

PMID:19549587

Authors

Meyer MR, Haas E, Prossnitz ER, Barton M

Title

Non-genomic regulation of vascular cell function and growth by estrogen.

Journal

Mol Cell Endocrinol 308:9-16 (2009)
DOI:10.1016/j.mce.2009.03.009

Reference

PMID:20694192

Authors

do Nascimento GR, Barros YV, Wells AK, Khalil RA

Title

Research into Specific Modulators of Vascular Sex Hormone Receptors in the Management of Postmenopausal Cardiovascular Disease.

Journal

Curr Hypertens Rev 5:283-306 (2009)
DOI:10.2174/157340209789587717

Reference

PMID:15695368

Authors

Bjornstrom L, Sjoberg M

Title

Mechanisms of estrogen receptor signaling: convergence of genomic and nongenomic actions on target genes.

Journal

Mol Endocrinol 19:833-42 (2005)
DOI:10.1210/me.2004-0486

Reference

PMID:16270355

Authors

Manavathi B, Kumar R

Title

Steering estrogen signals from the plasma membrane to the nucleus: two sides of the coin.

Journal

J Cell Physiol 207:594-604 (2006)
DOI:10.1002/jcp.20551

Reference

PMID:21844907

Authors

Prossnitz ER, Barton M

Title

The G-protein-coupled estrogen receptor GPER in health and disease.

Journal

Nat Rev Endocrinol 7:715-26 (2011)
DOI:10.1038/nrendo.2011.122

Reference

PMID:21742056

Authors

Meyer MR, Prossnitz ER, Barton M

Title

The G protein-coupled estrogen receptor GPER/GPR30 as a regulator of cardiovascular function.

Journal

Vascul Pharmacol 55:17-25 (2011)
DOI:10.1016/j.vph.2011.06.003

Reference

PMID:19767412

Authors

Maggiolini M, Picard D

Title

The unfolding stories of GPR30, a new membrane-bound estrogen receptor.

Journal

J Endocrinol 204:105-14 (2010)
DOI:10.1677/JOE-09-0242

Reference

PMID:19464786

Authors

Prossnitz ER, Maggiolini M

Title

Mechanisms of estrogen signaling and gene expression via GPR30.

Journal

Mol Cell Endocrinol 308:32-8 (2009)
DOI:10.1016/j.mce.2009.03.026

Reference

PMID:12650715

Authors

Kelly MJ, Qiu J, Wagner EJ, Ronnekleiv OK

Title

Rapid effects of estrogen on G protein-coupled receptor activation of potassium channels in the central nervous system (CNS).

Journal

J Steroid Biochem Mol Biol 83:187-93 (2002)
DOI:10.1016/S0960-0760(02)00249-2

Reference

PMID:9278514

Authors

Paech K, Webb P, Kuiper GG, Nilsson S, Gustafsson J, Kushner PJ, Scanlan TS

Title

Differential ligand activation of estrogen receptors ERalpha and ERbeta at AP1 sites.

Journal

Science 277:1508-10 (1997)
DOI:10.1126/science.277.5331.1508

Reference

PMID:12421825

Authors

Razandi M, Pedram A, Park ST, Levin ER

Title

Proximal events in signaling by plasma membrane estrogen receptors.

Journal

J Biol Chem 278:2701-12 (2003)
DOI:10.1074/jbc.M205692200

Reference

PMID:18755790

Authors

Roepke TA, Xue C, Bosch MA, Scanlan TS, Kelly MJ, Ronnekleiv OK

Title

Genes associated with membrane-initiated signaling of estrogen and energy homeostasis.

Journal

Endocrinology 149:6113-24 (2008)
DOI:10.1210/en.2008-0769

Reference

PMID:21779010

Authors

Thomas C, Gustafsson JA

Title

The different roles of ER subtypes in cancer biology and therapy.

Journal

Nat Rev Cancer 11:597-608 (2011)
DOI:10.1038/nrc3093

Related
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map04010

MAPK signaling pathway

map04020

Calcium signaling pathway

map04151

PI3K-Akt signaling pathway

map04270

Vascular smooth muscle contraction

map04727

GABAergic synapse

map04913

Ovarian steroidogenesis

KO pathway

ko04915

All links

Chemical substance (8)   
   KEGG COMPOUND (8)   
Gene (567205)   
   KEGG ORTHOLOGY (78)   
   RefGene (567127)   
Literature (22)   
   PubMed (22)   
All databases (567235)   

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