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Biochemistry (Moscow)

, Volume 80, Issue 10, pp 1227–1234 | Cite as

Competitive agonists and antagonists of steroid nuclear receptors: Evolution of the concept or its reversal

  • O. V. SmirnovaEmail author
Review

Abstract

The mechanisms displaying pure and mixed steroid agonist/antagonist activity as well as principles underlying in vivo action of selective steroid receptor modulators dependent on tissue or cell type including interaction with various types of nuclear receptors are analyzed in this work. Mechanisms of in vitro action for mixed agonist/antagonist steroids are discussed depending on: specific features of their interaction with receptor hormone-binding pocket; steroid-dependent allosteric modulation of interaction between hormone–receptor complex and hormone response DNA elements; features of interacting hormone–receptor complex with protein transcriptional coregulators; level and tissue-specific composition of transcriptional coregulators. A novel understanding regarding context-selective modulators replacing the concept of steroid agonists and antagonists is discussed.

Keywords

pure agonists and antagonists mixed agonists/antagonists steroid nuclear receptors steroid-sensitive DNA elements transcriptional coregulators 

Abbreviation

AF1, 2, 3

activation function 1, 2, 3

BF1, 2, 3

binding function 1, 2, 3

CBI

coactivator binding inhibitor

COSMO

context selective modulator

CTE

C-terminal extension

DAC

deacylcortivazol

DBD

DNA-binding domain

EC50

half-maximal effective concentration

ER

estrogen receptor

GR

glucocorticoid receptor

IC50

half-maximal inhibitory concentration

LBD

ligand-binding domain

NRAM

nuclear receptor alternate-site modulator

NTD

N-terminal domain

PAA

partial agonist activity

PR

progestin receptor

SERM

selective estrogen receptor modulator

SRE

steroid response element

SSRM

selective steroid receptor modulator

TAmax

maximum transcriptional activity

TIF2

transcription intermediary factor-2

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Copyright information

© Pleiades Publishing, Ltd. 2015

Authors and Affiliations

  1. 1.Biological FacultyLomonosov Moscow State UniversityMoscowRussia

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