scholarly journals Estrogen receptor 1 expression and methylation of Esr1 promoter in mouse fetal prostate mesenchymal cells induced by gestational exposure to bisphenol A or ethinylestradiol

2019 ◽  
Vol 5 (3) ◽  
Author(s):  
Ramji K Bhandari ◽  
Julia A Taylor ◽  
Jennifer Sommerfeld-Sager ◽  
Donald E Tillitt ◽  
William A Ricke ◽  
...  
Keyword(s):  
Estrogen Receptor ◽  
Bisphenol A ◽  
Oral Contraceptives ◽  
Primary Cultures ◽  
Prostate Gland ◽  
Mesenchymal Cells ◽  
Urogenital Sinus ◽  
Environmental Estrogen ◽  
Mouse Prostate

Abstract Fetal/neonatal environmental estrogen exposures alter developmental programing of the prostate gland causing onset of diseases later in life. We have previously shown in vitro that exposures to 17β-estradiol (E2) and the endocrine disrupting chemical bisphenol A, at concentrations relevant to human exposure, cause an elevation of estrogen receptor α (Esr1) mRNA in primary cultures of fetal mouse prostate mesenchymal cells; a similar result was observed in the fetal rat urogenital sinus. Effects of these chemicals on prostate mesenchyme in vivo are not well understood. Here we show effects in mice of fetal exposure to the estrogenic drug in mixed oral contraceptives, 17α-ethinylestradiol (EE2), at a concentration of EE2 encountered by human embryos/fetuses whose mothers become pregnant while on EE2-containing oral contraceptives, or bisphenol A at a concentration relevant to exposures observed in human fetuses in vivo. Expression of Esr1 was elevated by bisphenol A or EE2 exposures, which decreased the global expression of DNA methyltransferase 3A (Dnmt3a), while methylation of Esr1 promoter was significantly increased. These results show that exposures to the environmental estrogen bisphenol A and drug EE2 cause transcriptional and epigenetic alterations to expression of estrogen receptors in developing prostate mesenchyme in vivo.

Exposure to the environmental estrogen bisphenol A differentially modulated estrogen receptor-α and -β immunoreactivity and mRNA in male mouse testis

Life Sciences ◽  
2003 ◽  
Vol 72 (10) ◽  
pp. 1159-1169 ◽  
Author(s):  
Toshihiro Takao ◽  
Wakako Nanamiya ◽  
Hossein Pournajafi Nazarloo ◽  
Reiko Matsumoto ◽  
Koichi Asaba ◽  
...  
Keyword(s):  
Estrogen Receptor ◽  
Bisphenol A ◽  
Male Mouse ◽  
Estrogen Receptor Α ◽  
Mouse Testis ◽  
Environmental Estrogen

scholarly journals The bi-modal effects of estradiol on gonadotropin synthesis and secretion in female mice are dependent on estrogen receptor-α

2006 ◽  
Vol 191 (1) ◽  
pp. 309-317 ◽  
Author(s):  
Jonathan Lindzey ◽  
Friederike L Jayes ◽  
Mariana M Yates ◽  
John F Couse ◽  
Kenneth S Korach
Keyword(s):  
Estrogen Receptor ◽  
Negative Feedback ◽  
Primary Cultures ◽  
Estrogen Receptor Α ◽  
High Plasma ◽  
Pituitary Cells ◽  
Gonadotropin Secretion ◽  
Female Mice ◽  
Positive Effects

Depending on the estrous/menstrual cycle stage in females, ovarian-derived estradiol (E2) exerts either a negative or a positive effect on the hypothalamic–pituitary axis to regulate the synthesis and secretion of pituitary gonadotropins, LH, and FSH. To study the role of estrogen receptor-α (ERα) mediating these effects, we assessed the relevant parameters in adult wild-type (WT) and ERα-null (αERKO) female mice in vivo and in primary pituitary cell cultures. The αERKO mice exhibited significantly higher plasma and pituitary LH levels relative to WT females despite possessing markedly high levels of circulating E2. In contrast, hypothalamic GnRH content and circulating FSH levels were comparable between genotypes. Ovariectomy led to increased plasma LH in WT females but no further increase in αERKO females, while plasma FSH levels increased in both genotypes. E2 treatment suppressed the high plasma LH and pituitary Lhb mRNA expression in ovariectomized WT females but had no effect in αERKO. In contrast, E2 treatments only partially suppressed plasma FSH in ovariectomized WT females, but this too was lacking in αERKO females. Therefore, negative feedback on FSH is partially E2/ERα mediated but more dependent on ovarian-derived inhibin, which was increased threefold above normal in αERKO females. Together, these data indicate that E2-mediated negative feedback is dependent on functional ERα and acts to primarily regulate LH synthesis and secretion. Studies in primary cultures of pituitary cells from WT females revealed that E2 did not suppress basal or GnRH-induced LH secretion but instead enhanced the latter response, indicating that the positive influence of E2 on gonadotropin secretion may occur at the level of the pituitary. Once again this effect was lacking in αERKO gonadotropes in culture. These data indicate that the aspects of negative and positive effects of E2 on gonadotropin secretion are ERα dependent and occur at the level of the hypothalamus and pituitary respectively.

Anterior prostate epithelial AR inactivation modifies estrogen receptor expression and increases estrogen sensitivity

2011 ◽  
Vol 301 (4) ◽  
pp. E727-E735 ◽  
Author(s):  
Ulla Simanainen ◽  
Keely McNamara ◽  
Yan Ru Gao ◽  
Stephen McPherson ◽  
Reena Desai ◽  
...  
Keyword(s):  
Estrogen Receptor ◽  
Squamous Metaplasia ◽  
Receptor Expression ◽  
Epithelial Proliferation ◽  
Mouse Prostate ◽  
Estrogen Sensitivity ◽  
Androgen Withdrawal ◽  
Prostate Diseases ◽  
Prostate Growth

Androgens influence prostate growth and development, so androgen withdrawal can control progression of prostate diseases. Although estrogen treatment was originally used to induce androgen withdrawal, more recently direct estrogen effects on the prostate have been recognized, but the nature of androgen-estrogen interactions within the prostate remain poorly understood. To characterize androgen effects on estrogen sensitivity in the mouse prostate, we contrasted models of castration-induced androgen withdrawal in the prostate stromal and epithelial compartments with a prostate epithelial androgen receptor (AR) knockout (PEARKO) mouse model of selective epithelial AR inactivation. Castration markedly increased prostate epithelial estrogen receptor (ER)α immunoreactivity compared with very low ERα expression in intact males. Similarly, strong basal and luminal ERα expression was detected in PEARKO prostate of intact males, suggesting that epithelial AR activity regulated epithelial ERα expression. ERβ was strongly expressed in intact, castrated, and PEARKO prostate. However, strong clusters of epithelial ERβ positivity coincided with epithelial stratification in PEARKO prostate. In vivo estrogen sensitivity was increased in PEARKO males, with greater estradiol-induced prostate growth and epithelial proliferation leading to squamous metaplasia, featuring markedly increased epithelial proliferation, thickening, and keratinization compared with littermate controls. Our results suggest that ERα expression in the prostate epithelial cells is regulated by local, epithelia-specific, androgen-dependent mechanisms, and this imbalance in the AR- and ER-mediated signaling sensitizes the mature prostate to exogenous estrogens.

scholarly journals The different effects of endocrine-disrupting chemicals on estrogen receptor-mediated transcription through interaction with coactivator TRAP220 in uterine tissue

2003 ◽  
Vol 31 (3) ◽  
pp. 551-561 ◽  
Author(s):  
H Inoshita ◽  
H Masuyama ◽  
Y Hiramatsu
Keyword(s):  
Estrogen Receptor ◽  
Bisphenol A ◽  
Endocrine Disrupting Chemicals ◽  
Endocrine Function ◽  
Uterine Tissue ◽  
Present Evidence ◽  
Endocrine Disrupting Chemical ◽  
Positive Effects ◽  
Endocrine Disrupting

An endocrine-disrupting chemical (EDC) can alter endocrine functions through a variety of mechanisms, including nuclear receptor-mediated changes in protein synthesis, interference with membrane receptor binding, steroidogenesis or synthesis of other hormones. Although major chemicals have been shown to disrupt estrogenic actions mainly through their binding to estrogen receptor (ER) or androgen receptor, it is not clear how EDCs affect endocrine functions in vivo. We present evidence that the EDCs bisphenol A and phthalate activate ER-mediated transcription through interaction with TRAP220. Moreover, bisphenol A had positive effects on the interaction between ER-beta and TRAP220 and on the expression of ER-beta and TRAP220 compared with phthalate and estradiol in uterine tIssue. These data suggested that some EDCs might alter endocrine function through the change of the receptor and coactivator levels in uterine tIssue and through the different effect on the interaction between ERs and coactivator TRAP220.

scholarly journals 3,3′-Diindolylmethane Dose-Dependently Prevents Advanced Prostate Cancer

2019 ◽  
Author(s):  
Yufei Li ◽  
Nathaniel W. Mahloch ◽  
Nicholas J.E. Starkey ◽  
Mónica Peña-Luna ◽  
George E. Rottinghaus ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Estrogen Receptor ◽  
High Fat Diet ◽  
Estrogen Receptor Alpha ◽  
Estrogen Receptor Beta ◽  
Control Group ◽  
High Fat ◽  
Mouse Prostate

Abstract3,3′-Diindolylmethane (DIM) is an acid-derived dimer of indole-3-carbinol, found in many cruciferous vegetables, such as broccoli, and has been shown to inhibit prostate cancer (PCa) in several in vitro and in vivo models. We demonstrated that DIM stimulated both estrogen receptor alpha (ERα) and estrogen receptor beta (ERβ) transcriptional activities and propose that ERβ plays a role in mediating DIM’s inhibition on cancer cell growth. To further study the effects of DIM on inhibiting advanced PCa development, we tested DIM in TRAMP (TRansgenic Adenocarcinoma of the Mouse Prostate) mice. The control group of mice were fed a high fat diet. Three additional groups of mice were fed the same high fat diet supplemented with 0.04%, 0.2% and 1% DIM. Incidence of advanced PCa, poorly differentiated carcinoma (PDC), in the control group was 60%. 1% DIM dramatically reduced PDC incidence to 24% (p=0.0012), while 0.2% and 0.04% DIM reduced PDC incidence to 38% (p=0.047) and 45% (p=0.14) respectively. Though DIM did affect mice weights, statistical analysis showed a clear negative association between DIM concentration and PDC incidence with p=0.004, while the association between body weight and PDC incidence was not significant (p=0.953). In conclusion, our results show that dietary DIM can inhibit the most aggressive stage of prostate cancer at concentration lower than previously demonstrated, possibly working through an estrogen receptor mediated mechanism.

scholarly journals In Vivo Profiling of Estrogen Receptor/Specificity Protein-Dependent Transactivation

Endocrinology ◽  
2008 ◽  
Vol 149 (11) ◽  
pp. 5696-5705 ◽  
Author(s):  
Fei Wu ◽  
Rui Xu ◽  
Kyounghyun Kim ◽  
James Martin ◽  
Stephen Safe
Keyword(s):  
Estrogen Receptor ◽  
Bisphenol A ◽  
Luciferase Activity ◽  
Fold Increase ◽  
Transgenic Animals ◽  
Mouse Uterus ◽  
Ici 182,780 ◽  
Synthetic Estrogens ◽  
Specificity Protein

17β-Estradiol (E2) activates the estrogen receptor (ER) through multiple genomic and nongenomic pathways in various tissues/organs. ERα/specificity protein-dependent activation of E2-responsive genes containing GC-rich promoters has been identified in breast and other cancer cell lines, and in this study, we describe transgenic animals overexpressing a transgene containing three tandem GC-rich sites linked to a minimal TATA or thymidine kinase promoter and a luciferase gene. Several mouse lines expressing the transgenes were characterized and, in line 15, E2 induced a 9-fold increase in luciferase activity in the female mouse uterus, and the synthetic estrogens bisphenol A and nonylphenol also induced uterine luciferase activity. The pure antiestrogen ICI 182,780 induced luciferase activity in the mouse uterus, and similar results were observed for ICI 182,780 in breast cancer cells transfected with this construct. Differences in the ER agonist and antagonist activities of E2, nonylphenol, bisphenol A, and ICI 182,780 were investigated in the male testis and penis and the male and female stomach in line 15 transgenic mice. All of these tissues were hormone responsive; however, the patterns of induced or repressed luciferase activity were ligand structure, tissue, and sex dependent. These results demonstrate for the first time hormonal activation or repression of a GC-rich promoter in vivo, and the results suggest that the ERα/specificity protein pathway may contribute to E2-dependent induction and repression of genes.

scholarly journals Estradiol and Bisphenol A Stimulate Androgen Receptor and Estrogen Receptor Gene Expression in Fetal Mouse Prostate Mesenchyme Cells

2007 ◽  
Vol 115 (6) ◽  
pp. 902-908 ◽  
Author(s):  
Catherine A. Richter ◽  
Julia A. Taylor ◽  
Rachel L. Ruhlen ◽  
Wade V. Welshons ◽  
Frederick S. vom Saal
Keyword(s):  
Gene Expression ◽  
Estrogen Receptor ◽  
Androgen Receptor ◽  
Bisphenol A ◽  
Receptor Gene ◽  
Estrogen Receptor Gene ◽  
Fetal Mouse ◽  
Mouse Prostate ◽  
Mesenchyme Cells ◽  
Receptor Gene Expression

scholarly journals Estrogen receptor independent neurotoxic mechanism of bisphenol A, an environmental estrogen

2007 ◽  
Vol 8 (1) ◽  
pp. 27 ◽  
Author(s):  
Yoot Mo Lee ◽  
Min Jae Seong ◽  
Jae Woong Lee ◽  
Yong Kyung Lee ◽  
Tae Myoung Kim ◽  
...  
Keyword(s):  
Estrogen Receptor ◽  
Bisphenol A ◽  
Environmental Estrogen
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