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Versatility or promiscuity: the estrogen receptors, control of ligand selectivity and an update on subtype selective ligands.

Ng HW, Perkins R, Tong W, Hong H - Int J Environ Res Public Health (2014)

Bottom Line: The wide repertoire of ER actions is mediated mostly through ligand-activated transcription factors and many DNA response elements in most tissues and organs.Their versatility, however, comes with the drawback of promiscuous interactions with structurally diverse exogenous chemicals with potential for a wide range of adverse health outcomes.Finally, how nature controls ER specificity and how the subtle differences in receptor subtypes are exploited in pharmaceutical design to achieve binding specificity and subtype selectivity for desired biological response are discussed.

View Article: PubMed Central - PubMed

Affiliation: Division of Bioinformatics and Biostatistics, National Center for Toxicological Research, US Food and Drug Administration, 3900 NCTR Road, Jefferson, AR 72079, USA. Huiwen.Ng@fda.hhs.gov.

ABSTRACT
The estrogen receptors (ERs) are a group of versatile receptors. They regulate an enormity of processes starting in early life and continuing through sexual reproduction, development, and end of life. This review provides a background and structural perspective for the ERs as part of the nuclear receptor superfamily and discusses the ER versatility and promiscuity. The wide repertoire of ER actions is mediated mostly through ligand-activated transcription factors and many DNA response elements in most tissues and organs. Their versatility, however, comes with the drawback of promiscuous interactions with structurally diverse exogenous chemicals with potential for a wide range of adverse health outcomes. Even when interacting with endogenous hormones, ER actions can have adverse effects in disease progression. Finally, how nature controls ER specificity and how the subtle differences in receptor subtypes are exploited in pharmaceutical design to achieve binding specificity and subtype selectivity for desired biological response are discussed. The intent of this review is to complement the large body of literature with emphasis on most recent developments in selective ER ligands.

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Related in: MedlinePlus

Structures of natural estrogens: estradiol (E2, the most potent), estrone (E1) and estriol (E3). The four rings of the endogenous ligand, E2, are labelled A-D according to the widely accepted naming convention.
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ijerph-11-08709-f005: Structures of natural estrogens: estradiol (E2, the most potent), estrone (E1) and estriol (E3). The four rings of the endogenous ligand, E2, are labelled A-D according to the widely accepted naming convention.

Mentions: The ERs are the target of the natural estrogens, namely estradiol (E2, most potent) [83], estrone (E1) and estriol (E3). E2 is also commonly referred to as 17β-estradiol as it possesses the hydroxyl group at the carbon 17 position above the steroid plane (α and β indicate below and above the steroid plane, respectively) (Figure 5).


Versatility or promiscuity: the estrogen receptors, control of ligand selectivity and an update on subtype selective ligands.

Ng HW, Perkins R, Tong W, Hong H - Int J Environ Res Public Health (2014)

Structures of natural estrogens: estradiol (E2, the most potent), estrone (E1) and estriol (E3). The four rings of the endogenous ligand, E2, are labelled A-D according to the widely accepted naming convention.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4198987&req=5

ijerph-11-08709-f005: Structures of natural estrogens: estradiol (E2, the most potent), estrone (E1) and estriol (E3). The four rings of the endogenous ligand, E2, are labelled A-D according to the widely accepted naming convention.
Mentions: The ERs are the target of the natural estrogens, namely estradiol (E2, most potent) [83], estrone (E1) and estriol (E3). E2 is also commonly referred to as 17β-estradiol as it possesses the hydroxyl group at the carbon 17 position above the steroid plane (α and β indicate below and above the steroid plane, respectively) (Figure 5).

Bottom Line: The wide repertoire of ER actions is mediated mostly through ligand-activated transcription factors and many DNA response elements in most tissues and organs.Their versatility, however, comes with the drawback of promiscuous interactions with structurally diverse exogenous chemicals with potential for a wide range of adverse health outcomes.Finally, how nature controls ER specificity and how the subtle differences in receptor subtypes are exploited in pharmaceutical design to achieve binding specificity and subtype selectivity for desired biological response are discussed.

View Article: PubMed Central - PubMed

Affiliation: Division of Bioinformatics and Biostatistics, National Center for Toxicological Research, US Food and Drug Administration, 3900 NCTR Road, Jefferson, AR 72079, USA. Huiwen.Ng@fda.hhs.gov.

ABSTRACT
The estrogen receptors (ERs) are a group of versatile receptors. They regulate an enormity of processes starting in early life and continuing through sexual reproduction, development, and end of life. This review provides a background and structural perspective for the ERs as part of the nuclear receptor superfamily and discusses the ER versatility and promiscuity. The wide repertoire of ER actions is mediated mostly through ligand-activated transcription factors and many DNA response elements in most tissues and organs. Their versatility, however, comes with the drawback of promiscuous interactions with structurally diverse exogenous chemicals with potential for a wide range of adverse health outcomes. Even when interacting with endogenous hormones, ER actions can have adverse effects in disease progression. Finally, how nature controls ER specificity and how the subtle differences in receptor subtypes are exploited in pharmaceutical design to achieve binding specificity and subtype selectivity for desired biological response are discussed. The intent of this review is to complement the large body of literature with emphasis on most recent developments in selective ER ligands.

Show MeSH
Related in: MedlinePlus