Expression of estrogen receptor co-regulators SRC-1, RIP140 and NCoR and their interaction with estrogen receptor in rat uterus, under the influence of ormeloxifene

Daverey, Amita; Saxena, Ruchi; Tewari, Shikha; Goel, Sudhir K.; Dwivedi, Anila

doi:10.1016/j.jsbmb.2009.05.006

Cited by 10 publications

(5 citation statements)

References 54 publications

(62 reference statements)

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“…Two ERb variants are expressed in these cells, suggesting an ERb-mediated effect. Ormeloxifene appears to function by inhibiting the interaction of the coactivator SRC1 with ERa while enhancing the interaction with the coactivator RIP140 and corepressor NCoR as well as interaction of NCoR with ERb in the rat uterus (Daverey et al, 2009). Antimutagenic effects from treatment with ormeloxifene have also been described, as it reduces sister chromatid exchange and chromosome aberrations in female Swiss albino mice exposed to genotoxic compounds (Giri et al, 1999).…”

Section: Nuclear Receptors and Their Selective Modulatorsmentioning

confidence: 99%

Nuclear Receptors and Their Selective Pharmacologic Modulators

et al. 2013

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Section: Nuclear Receptors and Their Selective Modulatorsmentioning

confidence: 99%

Nuclear Receptors and Their Selective Pharmacologic Modulators

et al. 2013

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“…For instance, raloxifene promotes ERα interaction with NCoR1 both in vivo and in vitro [42]. In rat uterus, ormeloxifene antagonizes in vivo ERα activity by increasing the recruitment of NCoR1 corepressor and reducing the recruitment of SRC-1 coactivator [57]. In addition to SRCs, other coactivators can also play a role in SERM activity.…”

Section: Determination Of Serm Activity By Coactivators and Corepressorsmentioning

confidence: 99%

Nuclear receptor modulation – Role of coregulators in selective estrogen receptor modulator (SERM) actions

Feng

O’Malley

2014

Steroids

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Selective Estrogen Receptor Modulators (SERMs) are a class of small-molecule chemical compounds that bind to estrogen receptor (ER) ligand binding domain (LBD) with high affinity and selectively modulate ER transcriptional activity in a cell- and tissue-dependent manner. The prototype of SERMs is tamoxifen, which has agonist activity in bone, but has antagonist activity in breast. Tamoxifen can reduce the risk of breast cancer and, at same time, prevent osteoporosis in postmenopausal women. Tamoxifen is widely prescribed for treatment and prevention of breast cancer. Mechanistically the activity of SERMs is determined by the selective recruitment of coactivators and corepressors in different cell types and tissues. Therefore, understanding the coregulator function is the key to understanding the tissue selective activity of SERMs.

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“…100 , 101 Ormeloxifene has been found to inhibit ER binding to coactivator SRC-1 as well as DNA elements, thereby potently antagonizing estrogen-induced gene expression in the endometrium. 27 , 28 When given in combination with 17β-estradiol, ormeloxifene increased interactions of ERα with corepressors RIP140 and NCoR, and like BZA, decreased ERα expression. 28 Ormeloxifene modestly increases uterine wet weight in ovariectomized rats, suggesting mild agonist activity, but when given in combination with 17β-estradiol or ethynylestradiol the increase is significantly less than with either estrogen alone, albeit still greater than in control animals.…”

Section: Are Other Tsec Combinations Viable?mentioning

confidence: 99%

“… 27 , 28 When given in combination with 17β-estradiol, ormeloxifene increased interactions of ERα with corepressors RIP140 and NCoR, and like BZA, decreased ERα expression. 28 Ormeloxifene modestly increases uterine wet weight in ovariectomized rats, suggesting mild agonist activity, but when given in combination with 17β-estradiol or ethynylestradiol the increase is significantly less than with either estrogen alone, albeit still greater than in control animals. 26 - 29 Ormeloxifene has not been evaluated clinically as part of a TSEC.…”

Section: Are Other Tsec Combinations Viable?mentioning

confidence: 99%

Tissue selective estrogen complex (TSEC): a review

2018

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Objective:This review describes historical development of selective estrogen receptor modulators (SERMs) and their combination with estrogens, termed a tissue selective estrogen complex (TSEC), and considers the potential for future TSEC development.Methods:This narrative review is based on literature identified on PubMed and the TSEC research and development experience of the authors.Results:SERMs have estrogenic and antiestrogenic effects in various tissues; however, no single agent has achieved an optimal balance of agonist and antagonist effects for the treatment of menopausal symptoms. Clinically, a number of SERMs protect against osteoporosis and breast cancer but can exacerbate vasomotor symptoms. Estrogens alleviate menopausal hot flushes and genitourinary symptoms as well as reduce bone loss, but the addition of a progestogen to menopausal hormone therapy to protect against endometrial cancer increases vaginal bleeding risk, breast tenderness, and potentially breast cancer. The search for an effective menopausal therapy with better tolerability led to the investigation of TSECs. Clinical development of a TSEC consisting of conjugated estrogens/bazedoxifene increased understanding of the importance of a careful consideration of the combination's components and their respective doses to balance safety and efficacy. Bazedoxifene is an estrogen receptor agonist in bone but an antagonist/degrader in the endometrium, which has contributed to its success as a TSEC component. Other oral TSEC combinations studied thus far have not demonstrated similar endometrial safety.Conclusions:Choice of SERM, selection of doses, and clinical trial data evaluating safety and efficacy are key to ensuring safety and adequate therapeutic effect of TSECs for addressing menopausal symptoms.

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Expression of estrogen receptor co-regulators SRC-1, RIP140 and NCoR and their interaction with estrogen receptor in rat uterus, under the influence of ormeloxifene

Cited by 10 publications

References 54 publications

Nuclear Receptors and Their Selective Pharmacologic Modulators

Nuclear Receptors and Their Selective Pharmacologic Modulators

Nuclear receptor modulation – Role of coregulators in selective estrogen receptor modulator (SERM) actions

Tissue selective estrogen complex (TSEC): a review

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