Abstract
Estrogen receptors (ERs) are steroid receptors located in the cytoplasm and on the nuclear membrane. The sequence similarities of human ERα, mouse ERα, rat ERα, dog ERα, and cat ERα are above 90%, but structures of ERα may different among species. Estrogen can be agonist and antagonist depending on its target organs. This hormone play roles in several diseases including breast cancer. There are variety of the relative binding affinity (RBA) of ER and estrogen species in comparison to 17β-estradiol (E2), which is a natural ligand of both ERα and ERβ. The RBA of the estrogen species are as following: diethyl stilbestrol (DES)>hexestrol>dienestrol>17β-estradiol (E2)>17-estradiol>moxestrol>estriol (E3)>4-OH estradiol>estrone-3-sulfate. Estrogen mimetic drugs, selective estrogen receptor modulators (SERMs), have been used as hormonal therapy for ER positive breast cancer and postmenopausal osteoporosis. In the postgenomic era, in silico models have become effective tools for modern drug discovery. These provide three dimensional structures of many transmembrane receptors and enzymes, which are important targets of de novo drug development. The estimated inhibition constants (Ki) from computational model have been used as a screening procedure before in vitro and in vivo studies.
Highlights
Estrogen receptors (ERs) are steroid receptors located in the cytoplasm and on the nuclear membrane
The sequence similarities of human ERα, mouse ERα, rat ERα, dog ERα, and cat ERα are above 90%, but structures of ERα may different among species
There are variety of the relative binding affinity (RBA) of ER and estrogen species in comparison to 17β-estradiol (E2), which is a natural ligand of both ERα and ERβ
Summary
Estrogen receptors (ERs) are members of 7-transmembrane receptors such as steroid hormone receptor subfamily, G protein coupled receptor family, and nuclear hormone receptor superfamily. There are two subtypes of estrogen receptor; ERα and ERβ (Kuiper et al, 1997; Barkhem et al, 1998). The genes encoding ERs located on different chromosomes, which are species specific. ERα locates on chromosome 6th and ERβ on chromosome 14th in humans. ERs-ligands interaction are attributed to changing LBD conformation. Expressions of ERα are found abundantly in normal organs such as uterus, liver, vagina and pituitary (Kuiper et al, 1997; Osborne et al, 2000; Millanta et al, 2005; Illera et al, 2006). ERs bind to estrogen induce conformational change and downstream cascades. Estrogen involves in RNA synthesis, the expression of co-activators and/or co-repressors, and several protein synthesis. This steroid hormone regulates ovarian follicles growth, mammary gland development, and female fertility
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
