Oestrogen receptor binding

Oestrogen receptor binding/Reporter gene assay. 

Figure 13.1 The distribution of (a) chemical classes and (b) binding activity for the NCTR dataset. The oestrogen receptor binding activity is represented as RBA. The RBA for the endogenous ligand, 17p-estradiol, was set to 100.

Jarman M, Leung OT, Leclercq G, Devleeschouwer N, Stoessel S, Coombes RC, Skilton RA (1986) Analogues of tamoxifen the role of the basic side-chain. Applications of a whole-cell oestrogen-receptor binding assay to N-oxides and quaternary salts. Anticancer Dmg Des 1 259-268... 

It is not certain that all the effects of DES can be ascribed to its oestrogenic activity (that is to say, directly related to its ability to bind to the oestrogen receptor), but it would appear from experience with this compound that rodent assays are able to detect the relevant toxicological effects. What then was the... 

More subtle modes of action are also possible since the response to hormone receptor binding is complex and could be affected by chemical interference with receptor-related proteins, DNA methylation or histone acetylation. Dioxin (TCDD), for example, reduces the ability of the oestrogen-receptor complex to bind to the oestrogen response element of DNA, reducing gene transcription. ... 

Sutherland RL, Murphy LC, San Foo M, Green MD, Whybourne AM, Krozowski ZS (1980) High-affinity anti-oestrogen binding site distinct from the oestrogen receptor. Nature 288(5788) 273-275... 

Drugs that can be used to control tumour cell proliferation inhibit a variety of enzymes, including thymidylate synthase and topoisomerase (Chapter 20). The enzyme aromatase converts a ring in a steroid to an aromatic ring. It converts, for example, adrenal steroid hormones into female sex hormones, which bind to oestrogenic receptors in the ovary or breast and increase the risk of ovarian or breast cancer. Aromatase inhibitors are used to treat patients with breast or ovarian cancers that are sensitive to oestrogen. Unfortunately, none of the inhibitors is specific for enzymes in tumour cells and they can therefore have severe side-effects (Chapter 21). 

Gustafsson J.A., Carlquist M. Structure of the ligand-binding domain of oestrogen receptor beta in the presence of a partial agonist and a... 

Kay This is more George Coupland s domain. He doesn t know exactly how CO induces FT expression. He has CO oestrogen receptor in cell culture, and if you give it oestrogen it translocates to the nucleus and you see FT come on. There is no evidence that CO binds DNA. No one knows what the partner is or... 

Fulvestrant is a competitive oestrogen receptor antagonist which binds to the receptor in a competitive manner with an affinity similar to that of estradiol. Fulvestrant downregulates the oestrogen receptor in human breast cancer cells. It is marketed for treatments of hormone-dependent breast cancer (Fig. 59) [145]. 

Fig. 4. Specificity determined by availability of receptor binding regions of DNA. With an oestrogen (E) sensitive gene, the receptor complex binds to specific regions of DNA (steroid response element) which influences the efficiency of mRNA initiation. If the response element is blocked, the gene is unresponsive to the steroid.

---