Hormones receptor

The hormone receptor proteins are composed of several domains, the central domain being involved in DNA binding (DBD). It is a small, highly conserved domain which contains 65-70 residues, organised as two perpendicular helices and stabilised by two zinc ions. The DNA response elements (RE) consist of two hexameric half sites, arranged as a palindrome or a repeat, separated by a few base pairs. In the case of estrogen response element (ERE), the consensus 

A second simulation carried out one year later [80] appeared to vindicate partly this idea, since the inclusion of 30 counterions reduced overall DNA bending to 19°. This simulation concerned the ER protein dimer interacting with the consensus dimer sequence ERE-ERE or with a mixed GRE-ERE site. The results indicated that binding specificity and stability are conferred by a network of both direct and water mediated protein-DNA hydrogen bonds. With the consensus sequence, this network involves three water molecules, the residues Glu 25, Lys 28, Lys 32 and Arg 33 and several DNA bases. In the nonconsensus sequence, a fluctuating network of hydrogen bonds allows water molecules to enter the protein-DNA interface and two additional waters are located at the interface. The authors also noted that the interaction of the protein with the DNA backbone is weaker with the consensus site than with the non- 

Concerning the DNA deformation induced by the hormone repressors, the authors suggest that is could play a functional role in the hormone response mechanism. In both the cases they study, the DNA axis in has a simple bend in one plane, but is S-shaped when viewed in an orthogonal direction. A similar S-shaped bend is observed in the nucleosome, at the axis of dyad symmetry [81-83]. Optimal protein-DNA interactions between the histone octamer and DNA and between a hormone receptor dimer and DNA complex could thus be achieved simultaneously if the hormone receptor complex were positioned over the nucleosome dyad axis. Such positioning would also satisfy the preferred rotational phasing of nucleosomal DNA, with the minor groove oriented away from the histone octamer. 

The thermodynamics aspects of specific interactions involving two responsive elements, GRE and ERE, were treated in the simulations and fi-ee energy perturbation (FEP) calculations carried out for a GR-DBD monomer. Three half-site responsive elements were considered the specific GRE and ERE sequences and an intermediate sequence where base pair 3 (AT) in the GRE 

Early modelling of this system was carried out by Miaskiewicz and Orstein [96] who performed dynamic simulations on isolated TBP and on its complex with DNA. Their study showed that the protein underwent large hinge-bending movements between the two domains of the protein. These motions changed the angle between the domains from 150° (its value in the complex) to roughly 90°. 

---

Potcntiomctric Biosensors Potentiometric electrodes for the analysis of molecules of biochemical importance can be constructed in a fashion similar to that used for gas-sensing electrodes. The most common class of potentiometric biosensors are the so-called enzyme electrodes, in which an enzyme is trapped or immobilized at the surface of an ion-selective electrode. Reaction of the analyte with the enzyme produces a product whose concentration is monitored by the ion-selective electrode. Potentiometric biosensors have also been designed around other biologically active species, including antibodies, bacterial particles, tissue, and hormone receptors. 

Thyroid hormone receptors (THRs) are subdivided intoa and P types, each having two isoforms. In rat brain, THR, mRNA is present in hippocampus, hypothalmus, cortex, cerebellum, and amygdala. Thyroxine (l-T (284) and triiodothyronine (l-T ) (285) are endogenous ligands for the THRs. TRIAC (286) is a THR antagonist. Selective ligands for PPARs have yet to be identified (Table 16). 

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. ... 

The term endocrine disrupter (ED) has tended to be used for those chemicals which act specifically at the level of the hormone receptor present in the target cells of various organs. Such chemicals may either mimic the action of the natural hormone (agonistic activity) or are sufficiently similar in molecular shape to the naturally produced hormone to interfere with the interaction between the hormone and receptor, thus blocking or impeding the activation of the receptor (antagonsitic activity). Such effects may occur at very low concentrations (as with the endogenous hormone), compared with the concentrations normally required to elicit the more traditional toxic effects attributed to chemicals. Recently,... 

This review briefly summarises the available evidence on the relative potency of the phytoestrogens, and discusses the evidence that beneficial effects on human diseases may potentially arise from consumption of foodstuffs containing these compounds, with particular regard to those effects that have been suggested as possibly being related to the hormone-receptor mediated activities of the phytoestrogens. Certain causes for concern regarding these compounds are also addressed. 

Colorectal Cancer. Colorectal cancer occurs frequently in the UK population but is historically rare in Asia. Rates in Japan have, however, increased rapidly in recent years.Interestingly, there appears to be an association between oestrogen exposure and colon cancer risk has been shown to increase in women with increasing age of first live birth, and to decrease with increasing parity (number of children). In addition, many colon tumours express sex hormone receptors, and this is thought to play a part in development of the tumours. "... 

Table 2 Raw Data and Posterior Modes from Dirichlet Mixtures for a Six Amino Acid Segment of Nuclear Hormone Receptors ...

---