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


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.


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


AF1, 2, 3

activation function 1, 2, 3

BF1, 2, 3

binding function 1, 2, 3


coactivator binding inhibitor


context selective modulator


C-terminal extension




DNA-binding domain


half-maximal effective concentration


estrogen receptor


glucocorticoid receptor


half-maximal inhibitory concentration


ligand-binding domain


nuclear receptor alternate-site modulator


N-terminal domain


partial agonist activity


progestin receptor


selective estrogen receptor modulator


steroid response element


selective steroid receptor modulator


maximum transcriptional activity


transcription intermediary factor-2


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© Pleiades Publishing, Ltd. 2015

Authors and Affiliations

  1. 1.Biological FacultyLomonosov Moscow State UniversityMoscowRussia

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