Estrogen Receptors: Therapies Targeted to Receptor Subtypes

@article{Nilsson2011EstrogenRT,
  title={Estrogen Receptors: Therapies Targeted to Receptor Subtypes},
  author={S Nilsson and Jan-{\AA}ke Gustafsson},
  journal={Clinical Pharmacology \& Therapeutics},
  year={2011},
  volume={89}
}
Over the past two decades, we have learned that estrogens play important physiological roles not only in women but also in men and that the biological effects of estrogen are mediated by not one but two distinct estrogen receptors (ERs), ERα and ERβ. Our appreciation of the physiological importance of estrogen and the mechanisms by which it acts has significantly increased over the years; however, we are only now beginning to decipher the roles of ERα and ERβ in different organs and to… 
Estrogen Receptor Ligands: A Review (2013–2015)
TLDR
This paper provides a general review of ER ligands published in international journals patented between 2013 and 2015 and indicates that many different structural scaffolds may provide high-affinity compounds, provided that some basic structural requirements are present.
Estrogen receptors (ERα versus ERβ): friends or foes in human biology?
TLDR
Continuing efforts in the study of ERs have helped to more clearly define their role in disease and to develop novel, ER-targeted therapeutics.
G Protein-Coupled Estrogen Receptor, GPER1, Offers a Novel Target for the Treatment of Digestive Diseases
TLDR
The complex signaling pathways of three estrogen receptors are discussed, the development of GPER1-specific ligands are highlighted, and the latest advances in the role of GP ER1 in the pathogenesis of gallstone formation are summarized.
Selective estrogen receptor modulators: tissue specificity and clinical utility
TLDR
The mechanisms of SERM tissue specificity are discussed and the therapeutic application of well-known and emergent SERMs are highlighted, including thromboembolic events, that have proven to be obstacles in their clinical utility.
Distinct Role of Estrogen and Er (Α and Β) in Various Brain Disease Anomalies
Estrogens, the primary ovarian hormones and are accountable for the proliferation of cells and tissues linked to reproduction [1]. Along with the functions on female reproductive system, estrogens
International Union of Basic and Clinical Pharmacology. XCVII. G Protein–Coupled Estrogen Receptor and Its Pharmacologic Modulators
TLDR
The history and characterization of GPER over the past 15 years is described, focusing on the pharmacology of steroidal and nonsteroidal compounds that have been employed to unravel the biology of this most recently recognized estrogen receptor.
The many faces of estrogen signaling
TLDR
This review wishes to highlight the newer aspects of estrogen signaling that exceed its classical endocrine regulatory role, especially emphasizing its tight intertwinement with epigenetic mechanisms.
Design and Synthesis of Selective Estrogen Receptor β Agonists and Their Pharmacology
TLDR
The research in this dissertation involved the design of non-steroidal ERβ selective agonists for hippocampal memory consolidation and serves as a foundation for development of other cycloheptyl/hexyl based ERβ agonists or antagonists having acceptable pharmacological profiles.
...
...

References

SHOWING 1-10 OF 74 REFERENCES
Estrogen Receptors: Their Actions and Functional Roles in Health and Disease
TLDR
The cloning of coregulators and chromatin modulators together with sophisticated methodology to study gene regulation has significantly increased the understanding of cellular and target gene responses to estrogens, SERMs, and ER subtype-selective ligands.
Dissecting Physiological Roles of Estrogen Receptor α and β with Potent Selective Ligands from Structure-Based Design
TLDR
This work designed steroidal ligands that exploit the differences in size and flexibility of the two ligand binding cavities and synthesized and tested compounds predicted to bind preferentially to either ERα or ERβ, leading to highly ER isotype-selective and potent ligands.
Estrogen receptor β acts as a dominant regulator of estrogen signaling
TLDR
It is shown that co-localization and subsequent heterodimerization of ERα and ERβ may result in receptor activity distinct from that of ER homodimers, and that ERβ can act as a negative or positive dominant regulator of ER activity.
Dissecting physiological roles of estrogen receptor alpha and beta with potent selective ligands from structure-based design.
TLDR
In vivo experiments with rats were conducted using the ERalpha- and ERbeta-selective agonists in comparison to 17beta-estradiol, and it can be concluded that estrogen effects on the uterus, pituitary, bone, and liver are primarily mediated via ERalpha.
Characterization of the Biological Roles of the Estrogen Receptors, ERα and ERβ, in Estrogen Target Tissues in Vivo through the Use of an ERα-Selective Ligand
TLDR
Propyl pyrazole triol (PPT) was found to be as efficacious as 17α-ethinyl-17β-estradiol in stimulating uterine weight gain and up-regulating complement 3 gene expression and was also effective in the brain.
Structure-function relationship of estrogen receptor alpha and beta: impact on human health.
TLDR
Understanding the structural basis and the molecular mechanisms by which ER transduce E2 signals in target cells will allow to create new pharmacologic therapies aimed at the treatment of a variety of human diseases affecting the cardiovascular system, the reproductive system and the skeletal system.
Estrogen Actions in the Brain and the Basis for Differential Action in Men and Women: A Case for Sex-Specific Medicines
TLDR
This review focuses on sex dimorphisms in the ability of estradiol to influence synaptic plasticity, neurotransmission, neurodegeneration, and cognition, which, it is argued, are due in a large part to sex differences in the organization of the underlying circuitry.
Characterization of the biological roles of the estrogen receptors, ERalpha and ERbeta, in estrogen target tissues in vivo through the use of an ERalpha-selective ligand.
TLDR
The findings indicate that several physiologically relevant estrogen-induced tissue responses can be effectively evoked via ERalpha alone and demonstrate that ER subtype-selective ligands can play a valuable role in enhancing the authors' understanding of how estrogens work through the two ER subtypes.
Estrogen receptor beta acts as a dominant regulator of estrogen signaling.
TLDR
It is shown that co-localization and subsequent heterodimerization of ERalpha and ERbeta may result in receptor activity distinct from that of ER homodimers, and that ERbeta can act as a negative or positive dominant regulator of ER activity.
...
...