Long-term dietary isoflavone exposure enhances estrogen sensitivity of rat uterine responsiveness mediated through estrogen receptor α

Möller, Frank; Diel, Patrick; Zierau, Oliver; Hertrampf, Torsten; Maass, Juliane; Vollmer, Günter

doi:10.1016/j.toxlet.2010.03.1117

Cited by 54 publications

(34 citation statements)

References 47 publications

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“…Previous studies have shown that the isoflavone genistein had significant effects on uterine epithelial height and gene expression [19,20] . To further confirm the uterotrophic effects of ICS, we examined the epithelial cell height, number of glands, and expression of PCNA in the uterus.…”

Section: Discussionmentioning

confidence: 99%

Assessment of the estrogenic activities of chickpea (Cicer arietinum L) sprout isoflavone extract in ovariectomized rats

Hai

Wang

et al. 2013

Acta Pharmacol Sin

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Aim: Chickpea (Cicer arietinum L) is a traditional Uighur herb. In this study we investigated the estrogenic activities of the isoflavones extracted from chickpea sprouts (ICS) in ovariectomized rats. Methods: Ten-week-old virgin Sprague-Dawley female rats were ovariectomized (OVX). The rats were administered via intragastric gavage 3 different doses of ICS (20, 50, or 100 mg·kg -1 ·d -1 ) for 5 weeks. Their uterine weight and serum levels of 17β-estradiol (E 2 ), follicle stimulating hormone (FSH) and luteinizing hormone (LH) were measured. The epithelial height, number of glands in the uterus, and number of osteoclasts in the femur were histologically quantified, and the expression of proliferating cell nuclear antigen (PCNA) was assessed immunohistochemically. Bone structural parameters, including bone mineral density (BMD), bone volume/tissue volume (BV/TV), trabecular thickness (Tb.Th) and trabecular separation (Tb.Sp) were measured using Micro-CT scanning. Results: Treatments of OVX rats with ICS (50 or 100 mg·kg -1 ·d -1 ) produced significant estrogenic effects on the uteruses, including the increases in uterine weight, epithelial height and gland number, as well as in the expression of the cell proliferation marker PCNA. The treatments changed the secretory profile of ovarian hormones and pituitary gonadotropins: serum E 2 level was significantly increased, while serum LH and FSH levels were decreased compared with the vehicle-treated OVX rats. Furthermore, the treatments significantly attenuated the bone loss, increased BMD, BV/TV and Tb.Th and decreased Tb.Sp and the number of osteoclasts. Treatment of OVX rats with the positive control drug E 2 (0.25 mg·kg -1 ·d -1 ) produced similar, but more prominent effects.Conclusion: ICS exhibits moderate estrogenic activities as compared to E 2 in ovariectomized rats, suggesting the potential use of ICS for the treatment of menopausal symptoms and osteoporosis caused by estrogen deficiency.

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Section: Discussionmentioning

confidence: 99%

Assessment of the estrogenic activities of chickpea (Cicer arietinum L) sprout isoflavone extract in ovariectomized rats

Hai

Wang

et al. 2013

Acta Pharmacol Sin

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“…Thus, the effect of E 2 on SK1 activity would benefit from increased ASAH1 expression. Furthermore, long-term exposure to genistein was recently shown to enhance E 2 responsiveness in the rat uterus (84) and reverse the inhibitory Model pathway for genistein-induced ASAH1 transcription in MCF-7 cells. Genistein (GEN) activates GPR30, which signals through G␣ i to activate c-Src and subsequently the MAPK pathway.…”

Section: Discussionmentioning

confidence: 99%

Genistein Stimulates MCF-7 Breast Cancer Cell Growth by Inducing Acid Ceramidase (ASAH1) Gene Expression

Lucki

Sewer

2011

Journal of Biological Chemistry

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Sphingolipid metabolites, such as ceramide (Cer), sphingosine (SPH), and sphingosine 1-phosphate (S1P), contribute to multiple aspects of carcinogenesis including cell proliferation, migration, angiogenesis, and tumor resistance. The cellular balance between Cer and S1P levels, for example, is an important determinant of cell fate, with the former inducing apoptosis and the later mitogenesis. Acid ceramidase (ASAH1) plays a pivotal role in regulating the intracellular concentration of these two metabolites by hydrolyzing Cer into SPH, which is rapidly phosphorylated to form S1P. Genistein is a phytoestrogen isoflavone that exerts agonist and antagonist effects on the proliferation of estrogen-dependent MCF-7 cells in a dose-dependent manner, primarily as a ligand for estrogen receptors. Genistein can also activate signaling through GPR30, a G-protein-coupled cell surface receptor. Based on the relationship between bioactive sphingolipids and tumorigenesis, we sought to determine the effect of genistein on ASAH1 transcription in MCF-7 breast cancer cells. We show herein that nanomolar concentrations of genistein induce ASAH1 transcription through a GPR30-dependent, pertussis toxin-sensitive pathway that requires the activation of c-Src and extracellular signal regulated kinase 1/2 (ERK1/2). Activation of this pathway promotes histone acetylation and recruitment of phospho-estrogen receptor ␣ and specificity protein-1 to the ASAH1 promoter, ultimately culminating in increased ceramidase activity. Finally, we show that genistein stimulates cyclin B2 expression and cell proliferation in an ASAH1-dependent manner. Collectively, these data identify a mechanism through which genistein promotes sphingolipid metabolism and support a role for ASAH1 in breast cancer cell growth.

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“…Isoflavones in soybeans and soyfoods have diverse physiological functions due to structural similarities with human hormones, such as estrogen (1,2). Major isoflavones in soyfoods include the 3 aglycones of daidzein, genistein, and glycitein, and corresponding derivatives with β-glucosides, acetyl-β-glucosides, and malonyl-β-glucosides (3).…”

Section: Introductionmentioning

confidence: 99%

Changes in isoflavone profiles and antioxidant activities in isoflavone extracts from soybeans and soyfoods under riboflavin photosensitization

Seol

et al. 2015

Food Sci Biotechnol

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Isoflavone extracts from soybeans and soyfoods were treated with riboflavin photosensitization and changes in antioxidant activities of isoflavone extracts under riboflavin sensitization were determined using 2,2-diphenyl-1-picrylhydrazyl (DPPH), 2,2'-azino-bis(3-ethylbenzothiazoline-6-sulphonic acid) (ABTS), and ferric reducing antioxidant power (FRAP) assays. Extracts rich in malonyl derivatives, β-glucosides, and aglycones were prepared from raw, ovendried, and almond-incubated soybeans, and the fermented soyfoods cheongukjang and natto. As the period of visible light irradiation increased to 120 min, the total isoflavone content determined using HPLC decreased in all samples. Aglycones in almond-incubated extracts decreased by 77.5% after 120 min, and β-glucosides in oven-dried extracts decreased by 52.0%. The radical scavenging activity based on DPPH and ABTS assays significantly (p<0.05) decreased in most extracts, compared with controls. The reducing power in aglycone-and β-glucoside-rich extracts increased, whereas the reducing power in extracts with high malonyl forms was not significantly (p>0.05) increased after riboflavin sensitization.

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Long-term dietary isoflavone exposure enhances estrogen sensitivity of rat uterine responsiveness mediated through estrogen receptor α

Cited by 54 publications

References 47 publications

Assessment of the estrogenic activities of chickpea (Cicer arietinum L) sprout isoflavone extract in ovariectomized rats

Assessment of the estrogenic activities of chickpea (Cicer arietinum L) sprout isoflavone extract in ovariectomized rats

Genistein Stimulates MCF-7 Breast Cancer Cell Growth by Inducing Acid Ceramidase (ASAH1) Gene Expression

Changes in isoflavone profiles and antioxidant activities in isoflavone extracts from soybeans and soyfoods under riboflavin photosensitization

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