Estrogen Receptor Conformation Measured by Peptide Profiling to Predict Xenoestrogen Tissue Specific Activity.

Selective estrogen receptor modulators (SERMs) are a diverse group of compounds that bind with specific, high-affinity binding to the estrogen receptor (ER). Depending on the tissue, SERMs can act as either ER agonists or antagonists. Recent advances in ER biology have provided insight into possible mechanisms by which SERMs elicit these tissue-specific estrogen agonist and estrogen antagonist activities. The estrogen response pathway has been shown to differ among target tissues depending on various tissue and cellular factors, such as the ER subtype, the structure of the bound receptor–ligand complex, and the tissue-specific cellular transcriptional machinery. Clinically available SERMs include clomiphene, tamoxifen and toremifene, which are triphenylethylenes, and raloxifene, a benzothiophene. Raloxifene has estrogen agonist effects on bone, serum lipids, and arterial vasculature, and estrogen antagonist effects in breast and uterus. Clinical trial data for raloxifene is used to illustrate some of the mechanisms by which SERMs exert their tissue-specific estrogen agonist and estrogen antagonist effects. The complex pharmacology surrounding the tissue selectivity of SERMs is discussed.

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Effects of nonylphenol on estrogen receptor conformation, transcriptional activity and sexual reversion in rainbow trout (Oncorhynchus mykiss)

Aquatic Toxicology ◽

10.1016/s0166-445x(01)00164-3 ◽

2001 ◽

Vol 53 (3-4) ◽

pp. 173-186 ◽

Cited By ~ 37

Author(s):

T Madigou ◽

P Le Goff ◽

G Salbert ◽

J.P Cravedi ◽

H Segner ◽

...

Keyword(s):

Estrogen Receptor ◽

Rainbow Trout ◽

Oncorhynchus Mykiss ◽

Transcriptional Activity ◽

Rainbow Trout Oncorhynchus Mykiss ◽

Receptor Conformation

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Sphingolipid Profiling Reveals Different Extent of Ceramide Accumulation in Bovine Retroperitoneal and Subcutaneous Adipose Tissues

Metabolites ◽

10.3390/metabo10110473 ◽

2020 ◽

Vol 10 (11) ◽

pp. 473

Author(s):

Yue Hei Leung ◽

Sonja Christiane Bäßler ◽

Christian Koch ◽

Theresa Scheu ◽

Ulrich Meyer ◽

...

Keyword(s):

Insulin Sensitivity ◽

De Novo ◽

Specific Activity ◽

Multiple Reaction Monitoring ◽

De Novo Synthesis ◽

Bioactive Lipids ◽

Tissue Specific ◽

Sphingosine 1 Phosphate ◽

Ceramide Accumulation ◽

Subcutaneous Adipose

Sphingolipids are bioactive lipids that can modulate insulin sensitivity, cellular differentiation, and apoptosis in a tissue-specific manner. However, their comparative profiles in bovine retroperitoneal (RPAT) and subcutaneous adipose tissue (SCAT) are currently unknown. We aimed to characterize the sphingolipid profiles using a targeted lipidomics approach and to assess whether potentially related sphingolipid pathways are different between SCAT and RPAT. Holstein bulls (n = 6) were slaughtered, and SCAT and RPAT samples were collected for sphingolipid profiling. A total of 70 sphingolipid species were detected and quantified by UPLC-MS/MS in multiple reaction monitoring (MRM) mode, including ceramide (Cer), dihydroceramide (DHCer), sphingomyelin (SM), dihydrosphingomyelin (DHSM), ceramide-1-phosphate (C1P), sphingosine-1-phosphate (S1P), galactosylceramide (GalCer), glucosylceramide (GluCer), lactosylceramide (LacCer), sphinganine (DHSph), and sphingosine (Sph). Our results showed that sphingolipids of the de novo synthesis pathway, such as DHSph, DHCer, and Cer, were more concentrated in RPAT than in SCAT. Sphingolipids of the salvage pathway and the sphingomyelinase pathway, such as Sph, S1P, C1P, glycosphingolipid, and SM, were more concentrated in SCAT. Our results indicate that RPAT had a greater extent of ceramide accumulation, thereby increasing the concentration of further sphingolipid intermediates in the de novo synthesis pathway. This distinctive sphingolipid distribution pattern in RPAT and SCAT can potentially explain the tissue-specific activity in insulin sensitivity, proinflammation, and oxidative stress in RPAT and SCAT.

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Antioxidant and Antiapoptotic Activities of a Tissue-Specific Selective Estrogen Receptor Modulator, Idoxifene, in Rat Fibrotic Liver and Cultured Rat Hepatocytes

Trends in Gastroenterology and Hepatology ◽

10.1007/978-4-431-67895-3_67 ◽

2001 ◽

pp. 350-355

Author(s):

Ichiro Shimizu ◽

Toshihiro Omoya ◽

Yajun Zhou ◽

Mina Itonaga ◽

Hiroshi Inoue ◽

...

Keyword(s):

Estrogen Receptor ◽

Rat Hepatocytes ◽

Selective Estrogen Receptor Modulator ◽

Fibrotic Liver ◽

Tissue Specific ◽

Receptor Modulator ◽

Cultured Rat Hepatocytes

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Current and Evolving Approaches to Individualizing Estrogen Receptor-Based Therapy for Menopausal Women

The Journal of Clinical Endocrinology & Metabolism ◽

10.1210/jc.2013-3680 ◽

2014 ◽

Vol 99 (3) ◽

pp. 733-747 ◽

Cited By ~ 19

Author(s):

Richard J. Santen ◽

Risa Kagan ◽

Corrado J. Altomare ◽

Barry Komm ◽

Sebastian Mirkin ◽

...

Keyword(s):

Estrogen Receptor ◽

Postmenopausal Women ◽

English Language ◽

Specific Activity ◽

Evidence Synthesis ◽

Signs And Symptoms ◽

Estrogen Deficiency ◽

Menopausal Women ◽

Individualized Approach ◽

Meta Analyses

Context: Adding progestogens to estrogens changes the risk profile of hormonal therapy for menopausal women, and recent data support the need for progestogen-free options. Several current and evolving approaches to managing estrogen deficiency allow for progestogen omission. We review the mechanisms of estrogen activity and provide an overview of emerging and available estrogen receptor (ER)–based therapies. Evidence Acquisition: PubMed was searched for relevant English-language articles using keywords pertaining to estrogen deficiency, menopause, hormone therapy, and estrogen-only therapy. Pivotal or recent randomized controlled trials, large observational studies, comprehensive meta-analyses, and established therapeutic guidelines were compiled. Evidence Synthesis: Advances in our understanding of ER pharmacology have led to therapies designed to optimize ER activity, including selective ER modulators (SERMs) and tissue-selective estrogen complexes (TSECs). Each estrogen, SERM, and TSEC exhibits a unique profile of tissue-specific activity, spanning the spectrum from ER agonism to antagonism. Systemic estrogens unopposed by progestogens effectively manage menopausal symptoms in hysterectomized postmenopausal women but require progestogen use in postmenopausal women with a uterus. SERMs are effective for managing certain aspects of estrogen deficiency in postmenopausal women, but data suggest that pairing a SERM with estrogens to form a TSEC provides a more optimal therapeutic profile for women with a uterus. Conclusions: Treating signs and symptoms of estrogen deficiency requires an individualized approach based on a woman's goals and the purported risks of different therapies. New and emerging agents have demonstrated efficacy in postmenopausal women with a uterus, while allowing these women to avoid progestogens and their possible adverse effects.

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