Entry |
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Name |
Estrogen signaling pathway
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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.
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Class |
Organismal Systems; Endocrine system
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Pathway map |

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Disease |
H00708 | Naegeli-Franceschetti-Jadassohn syndrome |
H02061 | Estrogen resistance syndrome |
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Other DBs |
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Orthology |
K08550 | estrogen receptor alpha |
K04079 | molecular chaperone HtpG |
K09487 | heat shock protein 90kDa beta |
K03283 | heat shock 70kDa protein 1/2/6/8 |
K11255 | nuclear receptor coactivator 2 |
K02161 | apoptosis regulator Bcl-2 |
K22455 | estrogen receptor-binding fragment-associated gene 9 protein |
K08774 | transforming growth factor, alpha |
K08527 | retinoic acid receptor alpha |
K04379 | proto-oncogene protein c-fos |
K04448 | transcription factor AP-1 |
K04684 | transcription factor Sp1 |
K04246 | G-protein coupled estrogen receptor 1 |
K04632 | guanine nucleotide-binding protein G(s) subunit alpha |
K08523 | heparin-binding EGF-like growth factor |
K05870 | cyclic AMP-responsive element-binding protein 1 |
K04450 | cyclic AMP-dependent transcription factor ATF-2 |
K04374 | cyclic AMP-dependent transcription factor ATF-4 |
K09048 | cyclic AMP-responsive element-binding protein 3 |
K09047 | cyclic AMP-responsive element-binding protein 5 |
K09049 | cyclic AMP-dependent transcription factor ATF-6 beta |
K06279 | SHC-transforming protein 1 |
K17447 | SHC-transforming protein 2 |
K17448 | SHC-transforming protein 3 |
K17449 | SHC-transforming protein 4 |
K04364 | growth factor receptor-bound protein 2 |
K04366 | RAF proto-oncogene serine/threonine-protein kinase [EC:2.7.11.1] |
K00922 | phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha/beta/delta [EC:2.7.1.153] |
K02649 | phosphoinositide-3-kinase regulatory subunit alpha/beta/delta |
K04615 | gamma-aminobutyric acid type B receptor |
K04630 | guanine nucleotide-binding protein G(i) subunit alpha |
K04534 | guanine nucleotide-binding protein G(o) subunit alpha |
K04997 | potassium inwardly-rectifying channel subfamily J member 3 |
K05000 | potassium inwardly-rectifying channel subfamily J member 6 |
K05002 | potassium inwardly-rectifying channel subfamily J member 9 |
K04999 | potassium inwardly-rectifying channel subfamily J member 5 |
K04215 | mu-type opioid receptor |
K04634 | guanine nucleotide-binding protein G(q) subunit alpha |
K04958 | inositol 1,4,5-triphosphate receptor type 1 |
K04959 | inositol 1,4,5-triphosphate receptor type 2 |
K04960 | inositol 1,4,5-triphosphate receptor type 3 |
K04603 | metabotropic glutamate receptor 1 |
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Compound |
C01245 | D-myo-Inositol 1,4,5-trisphosphate |
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Reference |
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Authors |
Zhang D, Trudeau VL |
Title |
Integration of membrane and nuclear estrogen receptor signaling. |
Journal |
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Reference |
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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 |
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Reference |
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Authors |
McCarthy MM |
Title |
The two faces of estradiol: effects on the developing brain. |
Journal |
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Reference |
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Authors |
Kelly MJ, Ronnekleiv OK |
Title |
Membrane-initiated estrogen signaling in hypothalamic neurons. |
Journal |
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Reference |
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Authors |
Kelly MJ, Qiu J, Ronnekleiv OK |
Title |
Estrogen signaling in the hypothalamus. |
Journal |
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Reference |
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Authors |
Raz L, Khan MM, Mahesh VB, Vadlamudi RK, Brann DW |
Title |
Rapid estrogen signaling in the brain. |
Journal |
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Reference |
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Authors |
Malyala A, Kelly MJ, Ronnekleiv OK |
Title |
Estrogen modulation of hypothalamic neurons: activation of multiple signaling pathways and gene expression changes. |
Journal |
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Reference |
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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 |
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Reference |
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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 |
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Reference |
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Authors |
Meyer MR, Haas E, Prossnitz ER, Barton M |
Title |
Non-genomic regulation of vascular cell function and growth by estrogen. |
Journal |
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Reference |
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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 |
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Reference |
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Authors |
Bjornstrom L, Sjoberg M |
Title |
Mechanisms of estrogen receptor signaling: convergence of genomic and nongenomic actions on target genes. |
Journal |
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Reference |
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Authors |
Manavathi B, Kumar R |
Title |
Steering estrogen signals from the plasma membrane to the nucleus: two sides of the coin. |
Journal |
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Reference |
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Authors |
Prossnitz ER, Barton M |
Title |
The G-protein-coupled estrogen receptor GPER in health and disease. |
Journal |
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Reference |
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Authors |
Meyer MR, Prossnitz ER, Barton M |
Title |
The G protein-coupled estrogen receptor GPER/GPR30 as a regulator of cardiovascular function. |
Journal |
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Reference |
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Authors |
Maggiolini M, Picard D |
Title |
The unfolding stories of GPR30, a new membrane-bound estrogen receptor. |
Journal |
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Reference |
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Authors |
Prossnitz ER, Maggiolini M |
Title |
Mechanisms of estrogen signaling and gene expression via GPR30. |
Journal |
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Reference |
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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 |
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Reference |
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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 |
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Reference |
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Authors |
Razandi M, Pedram A, Park ST, Levin ER |
Title |
Proximal events in signaling by plasma membrane estrogen receptors. |
Journal |
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Reference |
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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 |
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Reference |
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Authors |
Thomas C, Gustafsson JA |
Title |
The different roles of ER subtypes in cancer biology and therapy. |
Journal |
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Related pathway |
ko04270 | Vascular smooth muscle contraction |
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LinkDB |
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