Determination of conformational changes in the progesterone receptor using ELISA-like assays

  title={Determination of conformational changes in the progesterone receptor using ELISA-like assays},
  author={M. Pullen and N. Laping and R. Edwards and J. Bray},
The conformation of proteins often influences their functional activity. The effect of progesterone receptor ligands on the C-terminal conformation of the progesterone receptor affects the recruitment of transcriptional cofactors. These conformations can be studied by differential sensitivity to proteolytic cleavage or immunoprecipitation with a conformation-specific antibody. This study describes an ELISA-like method using conformation-specific antibodies to the C-terminal or an area adjacent… Expand
The X-ray Structure of RU486 Bound to the Progesterone Receptor in a Destabilized Agonistic Conformation
Interestingly, B-factor analysis clearly shows that helix 12 becomes more flexible after RU486 binding, suggesting that RU486, being a model antagonist, does not induce one fixed conformation of Helix 12 but changes its positional equilibrium. Expand
A structural and in vitro characterization of asoprisnil: a selective progesterone receptor modulator.
The data suggest that asoprisnil differentially recruits coactivators and corepressors compared to RU486 or P4, and this specific cofactor interaction profile is apparently insufficient to oppose estrogenic activity in rat uterus. Expand
Global gene expression profiling of progesterone receptor modulators in T47D cells provides a new classification system
Global gene expression profiles demonstrated progesterone-independent effects for all PR modulators examined and emphasised similarities of asoprisnil and J1042 compared to J912 and all types of PR antagonists, further refines previous classification models and accentuates unique effects for each PR modulator. Expand
11-(pyridinylphenyl)steroids--a new class of mixed-profile progesterone agonists/antagonists.
A novel class of 11beta-[4-(heteroaryl)phenyl]-substituted pregnanes was identified that displayed the desired balance and was found to have a truly mixed activity, including a sizeable agonist component. Expand
The impact of progesterone and RU-486 on classic pro-labour proteins & contractility in human myometrial tissues during 24-hour exposure to tension & interleukin-1β
Overall, tissue stretch may, in part, regulate P4-sensitive pro-labour protein levels, but this is likely to be reliant on interaction with other in utero factors that were absent in the authors' tissue cultures. Expand
Medroxyprogesterone derivatives from microbial transformation as anti-proliferative agents and acetylcholineterase inhibitors (combined in vitro and in silico approaches)
The fungal transformations of medroxyrogesterone were investigated for the first time using Cunninghamella elegans, Trichothecium roseum, and Mucor plumbeus and the newly isolated biotransformed product 13 showed the most potent activity against proliferation of SH-SY5Y cells. Expand
Administration of depot medroxyprogesterone acetate on the day of mifepristone for medical abortion: a pilot study.
The timing of initiation of DMPA on the initial visit for medical abortion is satisfactory to women, but its influence on medical abortion efficacy requires further study. Expand
The title compound, C22H32O4, a fungal-transformed metabolite of medroxyprogesterone, comprises one cyclo­hexa­none ring, two cyclo­hexane rings and one cyclo­pentane ring fused together. TheExpand
The first successful experiments in Neutron Radiography were carried out (to our knowledge) in 1935, just a few years after the discovery of the neutron, by H. Kallmann and E. Kuhn using a smallExpand


Ligand-dependent conformational changes in the progesterone receptor are necessary for events that follow DNA binding.
The data imply that steroids induce a conformational change in their receptors which is necessary for events subsequent to DNA binding, most likely for transactivation. Expand
Effects of the steroid antagonist RU486 on dimerization of the human progesterone receptor.
The results suggest that RU486 induces a distinct conformational change both in PR monomers in solution and in dimers bound to DNA, and the capability to form heterodimers in vitro raises the possibility that the antagonist action of RU486 in vivo could in part be imposed in a dominant negative fashion through heterodimerization. Expand
Ligands induce conformational changes in the carboxyl-terminus of progesterone receptors which are detected by a site-directed antipeptide monoclonal antibody.
We have prepared a monoclonal antibody, C-262, to a synthetic peptide that contains the carboxy-terminal 14 amino acids from progesterone receptors (PR). This sequence is 100% conserved in allExpand
Induction of a novel conformation in the progesterone receptor by ZK299 involves a defined region of the carboxyl-terminal tail.
The results suggest that multiple types of antiprogestin can be defined in terms of their effects on the conformation of the carboxyl-terminal activation function of the progesterone receptor. Expand
The mechanism of RU486 antagonism is dependent on the conformation of the carboxy-terminal tail of the human progesterone receptor
It is suggested that the extreme C-terminal region of the receptor contains an inhibitory function that silences receptor transactivation in the absence of agonist and in the presence of antagonist. Expand
The antagonists RU486 and ZK98299 stimulate progesterone receptor binding to deoxyribonucleic acid in vitro and in vivo, but have distinct effects on receptor conformation.
Results are consistent with the conclusions that ZK98299 stimulates PR binding to target DNA sequences and that Zk98299 and RU486 represent two mechanistic classes of antagonists based on inducing different conformational changes in PR. Expand
16 alpha-substituted analogs of the antiprogestin RU486 induce a unique conformation in the human progesterone receptor resulting in mixed agonist activity.
It appears, therefore, that the observed differences in the activity of some PR and estrogen receptor ligands reflect the ability of the cellular transcription machinery to discriminate between the structurally different complexes that result following ligand interaction. Expand
Novel Mechanisms of Progesterone Antagonists and Progesterone Receptor
It is speculated that the different PR conformations induced by agonist and antagonists results in an asymmetric agonist/antagonist heterodimer that binds inefficiently to palindromic PREs. Expand
Hormone and antihormone induce distinct conformational changes which are central to steroid receptor activation.
It is concluded that transcriptional inactivation of steroid receptors by antihormones involves the induction of an inappropriate structural conformation at the extreme carboxyl terminus of the ligand binding domain. Expand
Progesterone receptor and the mechanism of action of progesterone antagonists
Both published and unpublished data supporting the concept of two types of progesterone antagonists are discussed, suggesting that in addition to behaving by classical competitive mechanisms these compounds (in particular Type II) may exhibit additional activity as transrepressors of PR in the same cell bound to hormone agonist. Expand