A comparative characterization of estrogens used in hormone therapy via estrogen receptor (ER)-α and -β

Perkins, Meghan S.; Toit, Renate Louw-du; Africander, Donita

doi:10.1016/j.jsbmb.2017.07.022

Cited by 26 publications

(28 citation statements)

References 108 publications

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“…Proponents of bHT claim that bE 3 and bE 1 are weaker, safer estrogens than bE 2 (Sites 2008, Chervenak 2009, Holtorf 2009 and that bE 3 antagonizes the potent estrogenic activity of bE 2 (Melamed et al 1997, Boothby et al 2004. However, we have recently shown that both bE 3 and bE 1 are not necessarily weaker estrogens than bE 2 in terms of transactivation and transrepression of gene expression, or their effects on breast cancer cell proliferation and anchorage-independent growth (Perkins et al 2017). Moreover, we showed that E 3 did not antagonize E 2 -induced gene expression, proliferation or anchorage-independent growth of the MCF-7 BUS breast cancer cell line (Perkins et al 2017).…”

Section: Custom-compounded Bioidentical Hormone Therapymentioning

confidence: 84%

Hormone therapy and breast cancer: emerging steroid receptor mechanisms

Perkins

Toit

Africander

2018

Journal of Molecular Endocrinology

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Although hormone therapy is widely used by millions of women to relieve symptoms of menopause, it has been associated with several side-effects such as coronary heart disease, stroke and increased invasive breast cancer risk. These side-effects have caused many women to seek alternatives to conventional hormone therapy, including the controversial custom-compounded bioidentical hormone therapy suggested to not increase breast cancer risk. Historically estrogens and the estrogen receptor were considered the principal factors promoting breast cancer development and progression, however, a role for other members of the steroid receptor family in breast cancer pathogenesis is now evident, with emerging studies revealing an interplay between some steroid receptors. In this review, we discuss examples of hormone therapy used for the relief of menopausal symptoms, highlighting the distinction between conventional hormone therapy and custom-compounded bioidentical hormone therapy. Moreover, we highlight the fact that not all hormones have been evaluated for an association with increased breast cancer risk. We also summarize the current knowledge regarding the role of steroid receptors in mediating the carcinogenic effects of hormones used in menopausal hormone therapy, with special emphasis on the influence of the interplay or crosstalk between steroid receptors. Unraveling the intertwined nature of steroid hormone receptor signaling pathways in breast cancer biology is of utmost importance, considering that breast cancer is the most prevalent cancer among women worldwide. Moreover, understanding these mechanisms may reveal novel prevention or treatment options, and lead to the development of new hormone therapies that does not cause increased breast cancer risk.

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Section: Custom-compounded Bioidentical Hormone Therapymentioning

confidence: 84%

Hormone therapy and breast cancer: emerging steroid receptor mechanisms

Perkins

Toit

Africander

2018

Journal of Molecular Endocrinology

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“…189 In the same study, estriol (E3) was found not to antagonize the activity of estradiol (E2) as claimed by many proponents of b(HT). 188,189 Also, both bioidentical estradiol (bE2) and estriol (bE3) used in [b(HT)] were found to be full estrogen agonists. 189 The grape flavonoid resveratrol directly binds to ERa with a more stable antagonistic conformation compared to low energy agonistic conformation.…”

Section: -94mentioning

confidence: 85%

“…In a recent study, Perkins et al . revealed that estrone (E1) has low affinity for ERβ and ethinyl estradiol (EE) has higher affinity for ERα . In the same study, estriol (E3) was found not to antagonize the activity of estradiol (E2) as claimed by many proponents of b(HT) .…”

Section: Determinants Of Bc Risk: Considerations For Bc Prevention Anmentioning

confidence: 90%

“…revealed that estrone (E1) has low affinity for ERβ and ethinyl estradiol (EE) has higher affinity for ERα . In the same study, estriol (E3) was found not to antagonize the activity of estradiol (E2) as claimed by many proponents of b(HT) . Also, both bioidentical estradiol (bE2) and estriol (bE3) used in [b(HT)] were found to be full estrogen agonists .…”

Section: Determinants Of Bc Risk: Considerations For Bc Prevention Anmentioning

confidence: 90%

“…188,189 Also, both bioidentical estradiol (bE2) and estriol (bE3) used in [b(HT)] were found to be full estrogen agonists. 189 The grape flavonoid resveratrol directly binds to ERa with a more stable antagonistic conformation compared to low energy agonistic conformation. 190 Apigenin exerts anticancer effects through ERb transactivation dependent mechanism in ERa 2 MDA-MB-231BC cells.…”

Section: -94mentioning

confidence: 99%

See 2 more Smart Citations

Translational opportunities for broad‐spectrum natural phytochemicals and targeted agent combinations in breast cancer

Nagaprashantha

Adhikari

Singhal

et al. 2017

Intl Journal of Cancer

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Breast cancer (BC) prevention and therapy in the context of life-style risk factors and biological drivers is a major focus of developmental therapeutics in oncology. Obesity, alcohol, chronic estrogen signaling and smoking have distinct BC precipitating and facilitating effects that may act alone or in combination. A spectrum of signaling events including enhanced oxidative stress and changes in estrogen-receptor (ER)-dependent and -independent signaling drive the progression of BC. Breast tumors modulate ERα/ERβ ratio, upregulate proliferative pathways driven by ERα and HER2 with a parallel loss and/or downregulation of tumor suppressors such as TP53 and PTEN which together impact the efficacy of therapeutic strategies and frequently lead to emergence of drug resistance. Natural phytochemicals modulate oxidative stress, leptin, integrin, HER2, MAPK, ERK, Wnt/β-catenin and NFκB signaling along with regulating ERα and ERβ, thereby presenting unique opportunities for both primary and combinatorial interventions in BC. In this regard, this article focuses on critical analyses of the evidence from multiple studies on the efficacy of natural phytochemicals in BC. In addition, areas in which the combinations of such effective natural phytochemicals with approved and/or developing anticancer agents can be translationally beneficial are discussed to derive evidence-based inference for addressing challenges in BC control and therapy.

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Long‐term hypogonadism diminishes the neuroprotective effects of dietary genistein in young adult ovariectomized rats after transient focal ischemia

Oppong-Gyebi

Metzger

Doan

et al. 2021

J of Neuroscience Research

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Increasing age disproportionately increases the risk of stroke among women compared to men of similar age, especially after menopause. One of the reasons for this observation is a sharp drop in circulating estrogens. However, the timing of initiation of estrogen replacement after menopause is associated with mixed beneficial and detrimental effects, hence contributing to widespread mistrust of estrogen use. Agents including soy isoflavones are being assessed as viable alternatives to estrogen therapy. In this study, we hypothesized that the neuroprotective effects of genistein, a soy isoflavone are less sensitive to the length of hypogonadism in young adult ovariectomized rats following cerebral ischemia. We expected that long‐term hypogonadism will worsen motor and cognitive function, increase post‐stroke inflammation with no effect on the neuroprotection of genistein. We compared the effect of treatment with dietary genistein (GEN) on short‐term (2 weeks) and long‐term hypogonadism (12 weeks) in young adult ovariectomized Sprague–Dawley rats on sensorimotor function, cognition and inflammation after focal ischemia. Dorsal Silastic implant of 17β‐estradiol (E2) was used as a control for hormone therapy. Long‐term hypogonadism stroked rats performed worse than the short‐term hypogonadism stroked rats on the motor and cognitive function tests. GEN did not improve neurological assessment and motor learning after either short‐term or long‐term hypogonadism. GEN improved cognitive flexibility after short‐term hypogonadism but not after the long‐term. Both GEN and E2 reduced tissue loss after short‐term hypogonadism and reduced GFAP expression at the contralateral side of ischemia after long‐term hypogonadism. The length of hypogonadism may differentially influence the neuroprotective effects of both GEN and E2 on the motor and cognitive functions in young adult rats.

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A comparative characterization of estrogens used in hormone therapy via estrogen receptor (ER)-α and -β

Cited by 26 publications

References 108 publications

Hormone therapy and breast cancer: emerging steroid receptor mechanisms

Hormone therapy and breast cancer: emerging steroid receptor mechanisms

Translational opportunities for broad‐spectrum natural phytochemicals and targeted agent combinations in breast cancer

Long‐term hypogonadism diminishes the neuroprotective effects of dietary genistein in young adult ovariectomized rats after transient focal ischemia

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