Exogenous Hormonal Regulation in Breast Cancer Cells by Phytoestrogens and Endocrine Disruptors

Abstract

Abstract:Observations on the role of ovarian hormones in breast cancer growth, as well as interest in contraception, stimulated research into the biology of estrogens. The identification of the classical receptors ER and ER and the transmembrane receptor GPER and the resolution of the structure of the ligand bound to its receptor established the principal molecular mechanisms of estrogen action. The presence of estrogen-like compounds in many plants used in traditional medicine or ingested as food ingredients, phytoestrogens, as well as the estrogenic activities of many industrial pollutants and pesticides, xenoestrogens, have prompted investigations into their role in human health. Phyto-and xenoestrogens bind to the estrogen receptors with a lower affinity than the endogenous estrogens and can compete or substitute the hormone. Xenoestrogens, which accumulate in the body throughout life, are believed to increase breast cancer risk, especially in cases of prenatal and prepuberal exposure whereas the role of phytoestrogens is still a matter of debate. At present, the application of phytoestrogens appears to be limited to the treatment of post-menopausal symptoms in women where the production of endogenous estrogens has ceased. In this review we discuss chemistry, structure and classification, estrogen signaling and the consequences of the interactions of estrogens, phytoestrogens and xenoestrogens with their receptors, the complex interactions of endogenous and exogenous ligands, the evaluation of the health risks related to xenoestrogens, and the perspectives toward the synthesis of potent third generation selective estrogen receptor modulators (SERMs).

Tamoxifen persistently disrupts the humoral adaptive immune response of gilthead seabream (Sparus aurata L.)

“…Vaccination promoted a strong decrease in gper mRNA levels, which may be related to the mobilization of acidophilic granulocytes from the head kidney to the vaccination/infection site (Chaves-Pozo et al, 2005b), since these cells expressed very high levels of gper (Cabas et al, 2013b). Notably, despite the fact that EE 2 and Tmx bind to GPER (Albini et al, 2014;Filardo et al, 2000;Prossnitz et al, 2008;Revankar et al, 2005), its expression was not further modulated by the treatment with these two compounds. In agreement with this is the previous observation that both in vitro and in vivo GPER activation by G1, a GPER selective agonist, failed to modulate the gene expression of gper (Cabas et al, 2013b).…”

Macromolecular Modelling and Docking Simulations for the Discovery of Selective GPER Ligands

“…To our knowledge, this is the first member of this class of molecules ever adopted as a potential lead compound. Overall, in the last years, several endogenous and exogenous compounds have been screened and their actual ability to bind to GPER determined (31,32,37,48). For instance, two benzopyrroloxazine derivatives, namely PBX1 and PBX2, demonstrated the ability to act as selective GPER antagonists (33).…”

Enzymatic intracrine regulation of white adipose tissue

“…In agreement, SHBG concentrations in blood inversely correlate with the abdominal fat mass in premenopausal women [110]. Dietary flavonoids and lignans, such as enterolactone, enterodiol and other phytoestrogens [111], have structural similarities with estrogen and can bind to ERs, preventing the binding of estrogens to the ERs and inhibiting Ar activity [112]. …”