Estrogen-Receptor Expression and Function in Female Reproductive Disease

There is no author summary for this article yet. Authors can add summaries to their articles on ScienceOpen to make them more accessible to a non-specialist audience.

Abstract

Estrogen receptors (ER) include ER alpha, ER beta and new membrane receptor G protein-coupled receptor 30 (GPR30). Estrogen receptors are key receptors to maintain ovarian granulosa cell differentiation, follicle and oocyte growth and development, and ovulation function. The abnormal functions of estrogen, its receptors, and estradiol synthesis-related enzymes are closely related to clinical reproductive endocrine diseases, such as polycystic ovary syndrome (PCOS) and endometriosis (EMS). At present, hormone therapy is the main treatment for ovarian-related diseases, and a stable hormone environment is established by regulating ovarian function. In recent years, some estrogen-related drugs have made great progress, such as clomiphene, which is a nonsteroidal antiestrogen drug in clinical application. This article elaborates on the regulatory role of estrogen and its nuclear receptors and membrane receptors in oocyte development, especially female reproductive diseases related to the abnormal expression of estrogen and its receptors. We also highlighted the latest advances of treatment strategy for these diseases and the application of related targeted small molecule drugs in clinical research and treatment, so as to provide reference for the treatment of female reproductive diseases.

Related collections

Most cited references 86

Record: found
Abstract: found
Article: not found

Comparison of the ligand binding specificity and transcript tissue distribution of estrogen receptors alpha and beta.

G G Kuiper, B. Carlsson, K Grandien … (1997)

The rat estrogen receptor (ER) exists as two subtypes, ER alpha and ER beta, which differ in the C-terminal ligand binding domain and in the N-terminal transactivation domain. In this study we investigated the messenger RNA expression of both ER subtypes in rat tissues by RT-PCR and compared the ligand binding specificity of the ER subtypes. Saturation ligand binding analysis of in vitro synthesized human ER alpha and rat ER beta protein revealed a single binding component for 16 alpha-iodo-17 beta-estradiol with high affinity [dissociation constant (Kd) = 0.1 nM for ER alpha protein and 0.4 nM for ER beta protein]. Most estrogenic substances or estrogenic antagonists compete with 16 alpha-[125I]iodo-17 beta-estradiol for binding to both ER subtypes in a very similar preference and degree; that is, diethylstilbestrol > hexestrol > dienestrol > 4-OH-tamoxifen > 17 beta-estradiol > coumestrol, ICI-164384 > estrone, 17 alpha-estradiol > nafoxidine, moxestrol > clomifene > estriol, 4-OH-estradiol > tamoxifen, 2-OH-estradiol, 5-androstene-3 beta, 17 beta-diol, genistein for the ER alpha protein and dienestrol > 4-OH-tamoxifen > diethylstilbestrol > hexestrol > coumestrol, ICI-164384 > 17 beta-estradiol > estrone, genistein > estriol > nafoxidine, 5-androstene-3 beta, 17 beta-diol > 17 alpha-estradiol, clomifene, 2-OH-estradiol > 4-OH-estradiol, tamoxifen, moxestrol for the ER beta protein. The rat tissue distribution and/or the relative level of ER alpha and ER beta expression seems to be quite different, i.e. moderate to high expression in uterus, testis, pituitary, ovary, kidney, epididymis, and adrenal for ER alpha and prostate, ovary, lung, bladder, brain, uterus, and testis for ER beta. The described differences between the ER subtypes in relative ligand binding affinity and tissue distribution could contribute to the selective action of ER agonists and antagonists in different tissues.

0 comments Cited 400 times – based on 0 reviews      Review now

Bookmark

Record: found
Abstract: not found
Article: not found

Cloning of a novel receptor expressed in rat prostate and ovary.

G G Kuiper, E Enmark, M Pelto-Huikko … (1996)

0 comments Cited 291 times – based on 0 reviews      Review now

Bookmark

Record: found
Abstract: found
Article: not found

Estrogen-induced activation of Erk-1 and Erk-2 requires the G protein-coupled receptor homolog, GPR30, and occurs via trans-activation of the epidermal growth factor receptor through release of HB-EGF.

A Frackelton, E J Filardo, J Quinn … (2000)

Estrogen rapidly activates the mitogen-activated protein kinases, Erk-1 and Erk-2, via an as yet unknown mechanism. Here, evidence is provided that estrogen-induced Erk-1/-2 activation occurs independently of known estrogen receptors, but requires the expression of the G protein-coupled receptor homolog, GPR30. We show that 17beta-estradiol activates Erk-1/-2 not only in MCF-7 cells, which express both estrogen receptor alpha (ER alpha) and ER beta, but also in SKBR3 breast cancer cells, which fail to express either receptor. Immunoblot analysis using GPR30 peptide antibodies showed that this estrogen response was associated with the presence of GPR30 protein in these cells. MDA-MB-231 breast cancer cells (ER alpha-, ER beta+) are GPR30 deficient and insensitive to Erk-1/-2 activation by 17beta-estradiol. Transfection of MDA-MB-231 cells with a GPR30 complementary DNA resulted in overexpression of GPR30 protein and conversion to an estrogen-responsive phenotype. In addition, GPR30-dependent Erk-1/-2 activation was triggered by ER antagonists, including ICI 182,780, yet not by 17alpha-estradiol or progesterone. Consistent with acting through a G protein-coupled receptor, estradiol signaling to Erk-1/-2 occurred via a Gbetagamma-dependent, pertussis toxin-sensitive pathway that required Src-related tyrosine kinase activity and tyrosine phosphorylation of tyrosine 317 of the Shc adapter protein. Reinforcing this idea, estradiol signaling to Erk-1/-2 was dependent upon trans-activation of the epidermal growth factor (EGF) receptor via release of heparan-bound EGF (HB-EGF). Estradiol signaling to Erk-1/-2 could be blocked by: 1) inhibiting EGF-receptor tyrosine kinase activity, 2) neutralizing HB-EGF with antibodies, or 3) down-modulating HB-EGF from the cell surface with the diphtheria toxin mutant, CRM-197. Our data imply that ER-negative breast tumors that continue to express GPR30 may use estrogen to drive growth factor-dependent cellular responses.

0 comments Cited 246 times – based on 0 reviews      Review now

Bookmark

All references

Author and article information

Journal

Journal ID (nlm-ta): Cells

Journal ID (iso-abbrev): Cells

Journal ID (publisher-id): cells

Title: Cells

Publisher: MDPI

ISSN (Electronic): 2073-4409

Publication date (Electronic): 21 September 2019

Publication date Collection: October 2019

Volume: 8

Issue: 10

Electronic Location Identifier: 1123

Affiliations

[1 ]Beijing Key Laboratory for Animal Genetic Improvement, National Engineering Laboratory for Animal Breeding, Key Laboratory of Animal Genetics and Breeding of the Ministry of Agriculture, College of Animal Science and Technology, China Agricultural University, Beijing 100193, China; S20183040519@ 123456cau.edu.cn (Z.-R.T.); zr123@ 123456cau.edu.cn (R.Z.)

[2 ]CAS Key Laboratory of Genome Sciences and Information, Beijing Institute of Genomics, Chinese Academy of Sciences, Beijing 100101, China

Author notes

[* ]Correspondence: lianzhx@ 123456cau.edu.cn (Z.-X.L.), popo84350746@ 123456163.com (S.-L.D.); young137@ 123456163.com (K.Y.); Tel.: +86-(010)-6273-3904 (Z.-X.L.); +86-(010)-8409-7698 (S.-L.D.); +86-(010)-6273-2681 (K.Y.)

[†]

These authors contributed equally to this work.

Author information

Shou-Long Deng https://orcid.org/0000-0003-1187-3037

Article

Publisher ID: cells-08-01123

DOI: 10.3390/cells8101123

PMC ID: 6830311

PubMed ID: 31546660

SO-VID: 41031a97-6cfb-4076-a129-640884ba9abd

License:

Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license ( http://creativecommons.org/licenses/by/4.0/).

Estrogen-Receptor Expression and Function in Female Reproductive Disease

Read this article at

Abstract

Related collections

Gamma Delta T cells

Most cited references 86

Comparison of the ligand binding specificity and transcript tissue distribution of estrogen receptors alpha and beta.

Cloning of a novel receptor expressed in rat prostate and ovary.

Estrogen-induced activation of Erk-1 and Erk-2 requires the G protein-coupled receptor homolog, GPR30, and occurs via trans-activation of the epidermal growth factor receptor through release of HB-EGF.

Author and article information

Journal

Affiliations

Author notes

Author information

Article

History

Categories

Comments

Comment on this article

Similar content 473

Cited by 56

Most referenced authors 1,355