Effects of the oestrogen receptor antagonist Fulvestrant on expression of genes that affect organization of the epididymal epithelium

Pereira, M. F. Neto; Fernandes, Sheilla Alessandra Ferreira; Nascimento, Aline Rosa; Siu, Erica Rosanna; Hess, Rex A.; Oliveira, Cleida A.; Porto, Catarina S.; Lazari, Maria Fatima Magalhães

doi:10.1111/j.2047-2927.2014.00219.x

Cited by 18 publications

(23 citation statements)

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“…5 ). GPER has been reported as a 43 kD protein in the rat testis [ 7 , 8 ] and a 55 kD protein in the epididymis of Wistar rats [ 10 ] and our antibody appears to detect both forms. Expression of the 43 kD protein appeared similar between epididymal regions while expression of the 55 kD band appeared stronger in the corpus and cauda compared with the IS/caput.…”

Section: Resultsmentioning

confidence: 58%

“…GPER is expressed by immature Sertoli cells, pachytene spermatocytes and round spermatids in the rat testis [ 6 – 8 ]. GPER has been reported to be present in the epididymis based on mRNA and western blot analysis [ 9 , 10 ] but GPER immunolocalization by region and cell type is still unknown. To better understand the role of GPER in epididymal function, this study was designed to determine the cellular and regional expression of GPER and investigate any difference between ages and strains of rats.…”

Section: Resultsmentioning

confidence: 99%

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Immunolocalization of G protein-coupled estrogen receptor in the rat epididymis

Martínez-Traverso

Pearl

2015

Reprod Biol Endocrinol

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BackgroundEstrogen plays an important role in male reproduction, and males lacking estrogen signaling in the reproductive tissues are infertile. Estrogen signaling is mediated via two nuclear receptors, ERα and ERβ, but it was recently found that a G protein-coupled estrogen receptor (GPER) is present in the testis. It is believed that GPER is a membrane form of the estrogen receptor and mediates non-classical estrogen signaling. However, the cellular localization of GPER in the epididymis is unknown. Therefore, the objective of this study was to determine the cellular and regional expression of GPER in the rat epididymis.FindingsTo localize expression, immunohistochemistry (IHC) was performed using fixed epididymal tissue. Three strains and ages of rats were used to identify whether GPER expression is strain or age specific. Our results are the first to demonstrate immunostaining of GPER in epididymal epithelial cells. Expression was highest near the apical membrane followed by the cytoplasm, consistent with a membrane bound receptor. The highest expression in adult rats was observed in corpus followed by cauda. Western blotting analysis of epididymal tissues from Sprague Dawley rats confirmed specificity of the antibody and regional expression.ConclusionsExpression of GPER in the corpus and cauda suggests a role for non-classical estrogen signaling in sperm maturation in the corpus, and sperm protection/storage in the cauda. GPER expression pre-pubertally suggests that estrogen may have a role in epithelial cell development in addition to regulation of adult function.

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Section: Resultsmentioning

confidence: 58%

Section: Resultsmentioning

confidence: 99%

Immunolocalization of G protein-coupled estrogen receptor in the rat epididymis

Martínez-Traverso

Pearl

2015

Reprod Biol Endocrinol

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“…Among these genes, aquaporin 9 contains both AREs and EREs, and its expression is regulated by both estrogen and androgen (Pastor-Soler et al 2010, Joseph et al 2011. Furthermore, we have also previously reported that treatment with the anti-estrogen fulvestrant affected the expression of proteins that are important for epithelial organization and absorption/secretion in the rat epididymis (Pereira et al 2014). This indicates that the balance of estrogen and androgen actions may be important to ensure proper epididymal function.…”

Section: Discussionmentioning

confidence: 96%

Estrogen receptor ESR1 mediates activation of ERK1/2, CREB, and ELK1 in the corpus of the epididymis

Cavalcanti

Lucas

Lazari

et al. 2015

Journal of Molecular Endocrinology

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Expression of the estrogen receptor ESR1 is higher in the corpus than it is in the initial segment/caput and cauda of the epididymis. ESR1 immunostaining in the corpus has been localized not only in the nuclei but also in the cytoplasm and apical membrane, which indicates that ESR1 plays a role in membrane-initiated signaling. The present study investigated whether ESR1 mediates the activation of rapid signaling pathways by estradiol (E 2 ) in the epididymis. We investigated the effect of E 2 and the ESR1-selective agonist (4,4 0 ,4 0 0 -(4-propyl-(1H)-pyrazole-1,3,5-triyl)trisphenol (PPT) on the activation of extracellular signal-regulated protein kinases (ERK1/2), CREB protein, and ETS oncogene-related protein (ELK1). Treatment with PPT did not affect ERK1/2 phosphorylation in the cauda, but it rapidly increased ERK1/2 phosphorylation in the initial segment/caput and corpus of the epididymis. PPT also activated CREB and ELK1 in the corpus of the epididymis. The PPT-induced phosphorylation of ERK1/2, CREB, and ELK1 was blocked by the ESR1-selective antagonist MPP and by pretreatment with a non-receptor tyrosine kinase SRC inhibitor, an EGFR kinase inhibitor, an MEK1/2 inhibitor, and a phosphatidylinositol-3-kinase inhibitor. In conclusion, these results indicate that the corpus, which is a region with high expression of the estrogen receptor ESR1, is a major target in the epididymis for the activation of rapid signaling by E 2 . The sequence of events that follow E 2 interaction with ESR1 includes the SRC-mediated transactivation of EGFR and the phosphorylation of ERK1/2, CREB, and ELK1. This rapid estrogen signaling may modulate gene expression in the corpus of the epididymis, and it may play a role in the dynamic microenvironment of the epididymal lumen.

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“…In Leydig cells the expression of GPER has been implicated in Sertoli cell proliferation, maturation and maintenance of fertility (Lucas et al, 2011(Lucas et al, , 2014. GPER1 signaling may also play a significant role in the epididymis (Pereyra-Martinez et al, 2001;Gomes et al, 2011;Pereira et al, 2014;Mart ınez-Traverso and Pearl 2015) and in post-testicular maturation of sperm (Gautier et al, 2016). GPER1-KO males are obese with dyslipidemia and insulin resistance (Haas et al, 2009;Sharma et al, 2013), phenotypes also seen in mice lacking ERa or aromatase.…”

Section: Discussionmentioning

confidence: 99%

Immunolocalization of G Protein‐Coupled Estrogen Receptor in the Pig Epididymis

Malivindi

Aquila

Rago

2018

The Anatomical Record

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The presence of estrogen in the genital ducts of different mammalian species has been extensively studied and the estrogen influence on the functional activity of the male genital tract has been hypothesized. Conversely, very few data have been reported on pig excurrent ducts: the localization of classical estrogen receptors (ERα and ERβ) is scarcely known, while the expression of the G protein-coupled receptor (GPER1), a membrane estrogen receptor, is still unknown in pig. The aim of the present study was to evaluate GPER1 expression in the different regions of the mature pig epididymis, using immunohistochemistry, western blot and RT-PCR analyses. The results showed that GPER1 is mainly expressed in the epithelial cells of the corpus epididymis compared to the caput and the cauda, while muscle cells are moderately immunostained and stromal cells are unstained. The presence of GPER1 was confirmed by Western blot and RT-PCR analyses. In our study, we have demonstrated for the first time the GPER1 expression in male porcine epididymis, revealing a new mediator of estrogen signaling at this site. In conclusion, these new data suggest that estrogen action via GPER1 may contribute to sperm maturation in the corpus and sperm protection/storage in the cauda. Interestingly, the presence of GPER1 in the muscle layer may be indicative of a possible GPER1 involvement in the estrogen regulation of duct contractility. Anat Rec, 2018. © 2018 Wiley Periodicals, Inc.

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Effects of the oestrogen receptor antagonist Fulvestrant on expression of genes that affect organization of the epididymal epithelium

Cited by 18 publications

References 85 publications

Immunolocalization of G protein-coupled estrogen receptor in the rat epididymis

Immunolocalization of G protein-coupled estrogen receptor in the rat epididymis

Estrogen receptor ESR1 mediates activation of ERK1/2, CREB, and ELK1 in the corpus of the epididymis

Immunolocalization of G Protein‐Coupled Estrogen Receptor in the Pig Epididymis

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