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Estrogen Hormone Biology

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Hamilton, Katherine J., Hewitt, Sylvia C., Arao, Yukitomo, Korach, Kenneth S.·2017·Current Topics in Developmental Biology

DOI 10.1016/bs.ctdb.2016.12.005

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Abstract

The hormone estrogen is involved in both female and male reproduction, as well as numerous other biological systems including the neuroendocrine, vascular, skeletal, and immune systems. Therefore, it is also implicated in many different diseases and conditions such as infertility, obesity, osteoporosis, endometriosis, and a variety of cancers. Estrogen works through its two distinct nuclear receptors, Estrogen Receptor alpha (ERα) and Estrogen Receptor beta (ERβ). Various transcriptional regulation mechanisms have been identified as the mode of action for estrogen, mainly the classical mechanism with direct DNA binding but also a non-genomic mode of action and one using tethered or indirect binding. The expression profiles of ERα and ERβ are unique with the primary sites of ERα expression being the uterus and pituitary gland and the main site of ERβ expression being the granulosa cells of the ovary. Mouse models with knockout or mutation of Esr1 and Esr2 have furthered our understanding of the role each individual receptor plays in physiology. From these studies, it is known that the primary roles for ERα are in the uterus and neuroendocrine system, as female mice lacking ERα are infertile due to impaired ovarian and uterine function, whereas female mice lacking ERβ are subfertile due to ovarian defects. The development of effective therapies for estrogen-related diseases has relied on an understanding of the physiological roles and mechanistic functionalities of ERα and ERβ in various human health and disease.

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Fontaine, C., Billon-Galés, A., Filipe, C., Douin‐Echinard, V., Fouque, M.-J., Flouriot, G., Gourdy, P., Lenfant, F., Laurell, H., Krust, A., et al. (2009) · HAL · Cited by 80
The AF-1 Activation Function of Estrogen Receptor α Is Necessary and Sufficient for Uterine Epithelial Cell Proliferation In Vivo
Abot, A., Fontaine, C., Raymond‐Letron, I., Flouriot, G., Adlanmérini, M., Buscato, M., Otto, C., Bergès, H., Laurell, H., Gourdy, P., et al. (2013) · Endocrinology · doi:10.1210/en.2012-2059 · Cited by 78
An Estrogen Receptor-α Knock-In Mutation Provides Evidence of Ligand-Independent Signaling and Allows Modulation of Ligand-Induced Pathways in Vivo
Sinkevicius, K. W., Burdette, J. E., Woloszyn, K., Hewitt, S. C., Hamilton, K. J., Sugg, S. L., Temple, K. A., Wondisford, F. E., Korach, K. S., Woodruff, T. K., et al. (2008) · Endocrinology · doi:10.1210/en.2007-1526 · Cited by 72
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The Absence of ER-β Results in Altered Gene Expression in Ovarian Granulosa Cells Isolated From In Vivo Preovulatory Follicles
Binder, A. K., Rodriguez, K. F., Hamilton, K. J., Stockton, P. S., Reed, C. E., & Korach, K. S. (2013) · Endocrinology · doi:10.1210/en.2012-2256 · Cited by 69
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Generation of Cyp17iCre transgenic mice and their application to conditionally delete estrogen receptor alpha (Esr1) from the ovary and testis
Bridges, P. J., Koo, Y., Kang, D. W., Hudgins‐Spivey, S., Lan, Z., Xu, X., DeMayo, F. J., Cooney, A. J., & Ko, C. J. (2008) · genesis · doi:10.1002/dvg.20428 · Cited by 68
Uterine Epithelial Cell Estrogen Receptor Alpha-Dependent and -Independent Genomic Profiles That Underlie Estrogen Responses in Mice1
Winuthayanon, W., Hewitt, S. C., & Korach, K. S. (2014) · Biology of Reproduction · doi:10.1095/biolreprod.114.120170 · Cited by 58
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The estrogen receptor antagonist ICI 182,780 can act both as an agonist and an inverse agonist when estrogen receptor α AF-2 is modified
Movérare‐Skrtic, S., Börjesson, A., Farman, H. H., Sjögren, K., Windahl, S. H., Lagerquist, M. K., Andersson, A., Stubelius, A., Carlsten, H., Gustafsson, J.-Α., et al. (2014) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1322910111 · Cited by 57
Interacting Quantitative Trait Loci Control Phenotypic Variation in Murine Estradiol-Regulated Responses
Roper, R. J., Griffith, J. S., Lyttle, C. R., Doerge, R. W., McNabb, A. W., Broadbent, R. E., & Teuscher, C. (1999) · Endocrinology · doi:10.1210/endo.140.2.6521 · Cited by 55
Generation of ERα-floxed and knockout mice using the Cre/LoxP system
Antonson, P., Omoto, Y., Humire, P., & Gustafsson, J.-Å. (2012) · Biochemical and Biophysical Research Communications · doi:10.1016/j.bbrc.2012.07.016 · Cited by 55
Novel DNA Motif Binding Activity Observed In Vivo With an Estrogen Receptor α Mutant Mouse
Hewitt, S. C., Li, L., Grimm, S. A., Winuthayanon, W., Hamilton, K. J., Pockette, B., Rubel, C. A., Pedersen, L. C., Fargo, D. C., Lanz, R. B., et al. (2014) · Molecular Endocrinology · doi:10.1210/me.2014-1051 · Cited by 54
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Hormones and Signaling
(1998) · Elsevier eBooks · doi:10.1016/b978-0-12-312411-1.x5000-8 · Cited by 47
The Naturally Occurring Luteinizing Hormone Surge Is Diminished in Mice Lacking Estrogen Receptor Beta in the Ovary1
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Selective Disruption of ERα DNA-Binding Activity Alters Uterine Responsiveness to Estradiol
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Transactivating function (AF) 2–mediated AF-1 activity of estrogen receptor α is crucial to maintain male reproductive tract function
Arao, Y., Hamilton, K. J., Goulding, E. H., Janardhan, K. S., Eddy, E. M., & Korach, K. S. (2012) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1216189110 · Cited by 39
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Estrogen receptor-mediated transcription involves the activation of multiple kinase pathways in neuroblastoma cells
Clark, S. M., Rainville, J. R., Zhao, X., Katzenellenbogen, B. S., Pfaff, D. W., & Vasudevan, N. (2013) · The Journal of Steroid Biochemistry and Molecular Biology · doi:10.1016/j.jsbmb.2013.09.010 · Cited by 38
The Intraovarian Actions of Estrogen Receptor-α Are Necessary to Repress the Formation of Morphological and Functional Leydig-Like Cells in the Female Gonad
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Estrogen Receptor α L543A,L544A Mutation Changes Antagonists to Agonists, Correlating with the Ligand Binding Domain Dimerization Associated with DNA Binding Activity
Arao, Y., Hamilton, K. J., Coons, L. A., & Korach, K. S. (2013) · Journal of Biological Chemistry · doi:10.1074/jbc.m113.463455 · Cited by 29
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Genetic control of estrogen‐regulated transcriptional and cellular responses in mouse uterus
Wall, E. H., Hewitt, S. C., Liu, L., del Río, R., Case, L. K., Lin, C., Korach, K. S., & Teuscher, C. (2013) · The FASEB Journal · doi:10.1096/fj.12-213462 · Cited by 21
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Impact of Ovarian Sex Steroids on Ovulation and Ovulatory Gene Induction in Aromatase-Null Mice
Toda, K., Hayashi, Y., Ono, M., & Saibara, T. (2011) · Endocrinology · doi:10.1210/en.2011-1462 · Cited by 18
Research Resource: Comparison of Gene Profiles From Wild-Type ERα and ERα Hinge Region Mutants
Burns, K. A., Li, Y., Liu, L., & Korach, K. S. (2014) · Molecular Endocrinology · doi:10.1210/me.2014-1122 · Cited by 14
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Genetic Control of Ductal Morphology, Estrogen-Induced Ductal Growth, and Gene Expression in Female Mouse Mammary Gland
Wall, E. H., Case, L. K., Hewitt, S. C., Nguyen-Vu, T., Candelaria, N. R., Teuscher, C., & Lin, C. (2014) · Endocrinology · doi:10.1210/en.2013-1910 · Cited by 10
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Estrogen receptor signaling mechanisms
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Enhancing the therapeutic efficacy of nanoparticles for cancer treatment using versatile targeted strategies
Tian, H., Zhang, T., Qin, S., Huang, Z., Zhou, L., Shi, J., Nice, E. C., Xie, N., Huang, C., & Shen, Z. (2022) · Journal of Hematology & Oncology · doi:10.1186/s13045-022-01320-5 · Cited by 426
Shaping Microglial Phenotypes Through Estrogen Receptors: Relevance to Sex-Specific Neuroinflammatory Responses to Brain Injury and Disease
Acosta-Martínez, M. (2020) · The Journal of Pharmacology and Experimental Therapeutics · doi:10.1124/jpet.119.264598 · Cited by 51
Prenatal exposure to PFAS, associations with preterm birth and modification by maternal estrogen levels: the maoming birth study
Qin, X.-D., Zhou, Y., Bloom, M. S., Qian, Z. (., Geiger, S. D., Vaughn, M. G., Chu, C., Li, Q.-Q., Yang, B.-Y., Hu, L.-W., et al. (2023) · Environmental Health Perspectives · doi:10.1289/ehp11377 · Cited by 45
CL316,243 and skeletal muscle metabolism: Role of sex and estrogen receptor beta
Maloney, A., Lee, J., Queathem, E. D., Schaller, K. A., Buckhary, S., Lubahn, D. B., Valentine, R. J., & Vieira-Potter, V. J. (2025) · Journal of Endocrinology · doi:10.1530/joe-25-0005 · Cited by 1

See all 336

Authors: Hamilton, K. J., Hewitt, S. C., Arao, Y., & Korach, K. S.
Venue: Current Topics in Developmental Biology
Publisher: Elsevier
Published: 2017
Volume: 125
Pages: 109-146
ISSN: 0070-2153 (ISSN-L)
DOI: 10.1016/bs.ctdb.2016.12.005
OpenAlex: W2583201344
Cited by: 336
References: 103
FWCI: 65.60
Type: book chapter
Language: en
Open access: green

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Estrogen Hormone Biology

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