Tamoxifen Regulation of Bone Growth and Endocrine Function in the Ovariectomized Rat: Discrimination of Responses Involving Estrogen Receptor α/Estrogen Receptor β, G Protein-Coupled Estrogen Receptor, or Estrogen-Related Receptor γ Using Fulvestrant (ICI 182780)

2011 ◽  
Vol 338 (1) ◽  
pp. 246-254 ◽  
Author(s):  
James M. Fitts ◽  
Robert M. Klein ◽  
C. Andrew Powers
Author(s):  
Hande Mefkure Ozkaya ◽  
Muge Sayitoglu ◽  
Nil Comunoglu ◽  
Eda Sun ◽  
Fatma Ela Keskin ◽  
...  

Abstract Purpose To evaluate the expression of G-protein coupled estrogen receptor (GPER1), aromatase, estrogen receptor α (ERα), estrogen receptor β (ERβ), pituitary tumor transforming gene (PTTG), and fibroblast growth factor 2 (FGF2) in GH-secreting and non-functioning adenomas (NFA). Methods Thirty patients with acromegaly and 27 patients with NFA were included. Gene expression was determined via quantitative reverse transcription polymerase chain reaction (QRT-PCR). Protein expression was determined via immunohistochemistry. Results There was no difference, in terms of gene expression of aromatase, ERα, PTTG, and FGF2 between the two groups (p>0.05 for all). ERβ gene expression was higher and GPER1 gene expression was lower in GH-secreting adenomas than NFAs (p<0.05 for all). Aromatase and ERβ protein expression was higher in GH-secreting adenomas than NFAs (p=0.01). None of the tumors expressed ERα. GPER1 expression was detected in 62.2% of the GH-secreting adenomas and 45% of NFAs. There was no difference in terms of GPER1, PTTG, FGF2 H scores between the two groups (p>0.05 for all). GPER1 gene expression was positively correlated to ERα, ERβ, PTTG, and FGF2 gene expression (p<0.05 for all). There was a positive correlation between aromatase and GPER1 protein expression (r=0.31; p=0.04). Conclusions GPER1 is expressed at both gene and protein level in a substantial portion of GH-secreting adenomas and NFAs. The finding of a positive correlation between GPER1 and ERα, ERβ, PTTG, and FGF2 gene expression and aromatase and GPER1 protein expression suggests GPER1 along with aromatase and classical ERs might mediate the effects of estrogen through upregulation of PTTG and FGF2.


2018 ◽  
Vol 28 (3) ◽  
pp. 500-504 ◽  
Author(s):  
Jenna Z. Marcus ◽  
Merieme Klobocista ◽  
Rouzan G. Karabakhtsian ◽  
Eric Prossnitz ◽  
Gary L. Goldberg ◽  
...  

ObjectiveThis study aimed to identify the hormonal receptor status in uterine adenosarcoma (AS) and uterine AS with sarcomatous overgrowth (AS + SO), including those with high-grade histologic features (nuclear pleomorphism, atypical mitoses, necrosis), with or without heterologous elements. Estrogen receptor (ER) status, including estrogen receptor α (ERα), estrogen receptor β (ERβ), and G protein–coupled estrogen receptor (GPER), and progesterone receptor (PgR) status were examined.MethodsFrom August 2001 to November 2013, 11 patients with histologic diagnosis of uterine AS were identified. Tumor tissue sections were stained for ERα, ERβ, GPER, and PgR and examined both for percentage of overall cells stained and for intensity of staining. Descriptive statistics were calculated using clinicopathologic data abstracted from the medical record.ResultsEight cases of AS and 3 cases of AS with high-grade features were identified. Seven of 8 tumor samples of AS showed strong or moderate intensity immunostaining for ERα; all AS + SO tumor samples showed minimal to no immunoreactivity for ERα. There was a significant decrease in ERαHscores in high-grade tumors when compared with AS (P= 0.01). Lower PgRHscores were observed in high-grade tumors compared with those in AS (P= 0.04). Estrogen receptor β immunostaining was variable, and GPER immunostaining was absent in the majority of tumor samples.ConclusionsHigher expression of ERα and PgR was observed in AS when compared with those with AS + SO and high-grade features. Both tumor subtypes showed similar levels of ERβ and GPER expression, although significant differences in ERβ and GPER expression were not detected. In contrast to our previous findings in uterine carcinosarcoma, ERs ERβ and GPER do not seem to play a significant role in AS in this study.


2015 ◽  
Vol 58 ◽  
pp. 51-66 ◽  
Author(s):  
Kelsy Sharice Jean Ervin ◽  
Erin Mulvale ◽  
Nicola Gallagher ◽  
Véronique Roussel ◽  
Elena Choleris

Endocrinology ◽  
2016 ◽  
Vol 157 (5) ◽  
pp. 1980-1990 ◽  
Author(s):  
Ulrike Klenke ◽  
Stephanie Constantin ◽  
Susan Wray

Abstract Peripheral feedback of gonadal estrogen to the hypothalamus is critical for reproduction. Bisphenol A (BPA), an environmental pollutant with estrogenic actions, can disrupt this feedback and lead to infertility in both humans and animals. GnRH neurons are essential for reproduction, serving as an important link between brain, pituitary, and gonads. Because GnRH neurons express several receptors that bind estrogen, they are potential targets for endocrine disruptors. However, to date, direct effects of BPA on GnRH neurons have not been shown. This study investigated the effects of BPA on GnRH neuronal activity using an explant model in which large numbers of primary GnRH neurons are maintained and express many of the receptors found in vivo. Because oscillations in intracellular calcium have been shown to correlate with electrical activity in GnRH neurons, calcium imaging was used to assay the effects of BPA. Exposure to 50μM BPA significantly decreased GnRH calcium activity. Blockage of γ-aminobutyric acid ergic and glutamatergic input did not abrogate the inhibitory BPA effect, suggesting direct regulation of GnRH neurons by BPA. In addition to estrogen receptor-β, single-cell RT-PCR analysis confirmed that GnRH neurons express G protein-coupled receptor 30 (G protein-coupled estrogen receptor 1) and estrogen-related receptor-γ, all potential targets for BPA. Perturbation studies of the signaling pathway revealed that the BPA-mediated inhibition of GnRH neuronal activity occurred independent of estrogen receptors, GPER, or estrogen-related receptor-γ, via a noncanonical pathway. These results provide the first evidence of a direct effect of BPA on GnRH neurons.


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