scholarly journals The Effects of Endocrine Disrupting Chemicals on Biomarkers of Inflammation Produced by Lipopolysaccharide Stimulated RAW264.7 Macrophages

2019 ◽  
Vol 16 (16) ◽  
pp. 2914
Author(s):  
Vedastus W. Makene ◽  
Edmund J. Pool
Keyword(s):  
Estrogen Receptor ◽  
Receptor Antagonist ◽  
Cell Cultures ◽  
Endocrine Disrupting Chemicals ◽  
Raw264.7 Cells ◽  
Inhibitory Effects ◽  
Receptor Antagonists ◽  
Estrogen Receptor Antagonist ◽  
Endocrine Disrupting ◽  
Raw264.7 Cell

Endocrine disrupting chemicals (EDCs) are common pollutants in the environment and can induce disruption of the endocrine and immune systems. The present study evaluated the effects of selected common environmental EDCs on secretion of inflammatory biomarkers by RAW264.7 cells. The EDCs investigated were Estradiol (E2), 5α-dihydrotestosterone (DHT), and Bisphenol A (BPA). To evaluate if the effects caused by EDCs were modulated by steroid hormone receptors, antagonists of estrogen and androgen receptors were used. The steroid receptor antagonists used were Tamoxifen, an estrogen receptor antagonist, and Flutamide, an androgen receptor antagonist. Secretion of biomarkers of inflammation, namely nitric oxide (NO) and interleukin 6 (IL-6), were monitored. The NO was determined using Griess reaction and IL-6 was measured by enzyme linked immunosorbent assay (ELISA). Although 5 μg/mL E2, DHT, and BPA were not toxic to RAW264.7 cell cultures, the same treatments significantly (p < 0.001) reduced both NO and IL-6 secretion by lipopolysaccharide (LPS)-stimulated RAW264.7 cell cultures. The suppression of NO and IL-6 secretion indicate inhibition of inflammation by DHT, E2, and BPA. The inhibitory effects of DHT, E2 and BPA are partially mediated via their cellular receptors, because the effects were reversed by their respective receptor antagonists. Flutamide reversed the effects of DHT, while Tamoxifen reversed the effects of E2 and BPA. In conclusion, E2, BPA, and DHT inhibit the synthesis of inflammation biomarkers by LPS-stimulated RAW264.7 cells. The inhibitory effects of EDCs can be partially reversed by the addition of an estrogen receptor antagonist for E2 and BPA, and an androgenic receptor antagonist for DHT. The inhibition of inflammatory response in stimulated RAW264.7 cells may be a useful bioassay model for monitoring estrogenic and androgenic pollutants.

scholarly journals Chemical space, diversity and activity landscape analysis of estrogen receptor binders

RSC Advances ◽  
2018 ◽  
Vol 8 (67) ◽  
pp. 38229-38237 ◽  
Author(s):  
J. Jesús Naveja ◽  
Ulf Norinder ◽  
Daniel Mucs ◽  
Edgar López-López ◽  
Josė L. Medina-Franco
Keyword(s):  
Estrogen Receptor ◽  
Chemical Space ◽  
Endocrine Disrupting Chemicals ◽  
Landscape Analysis ◽  
Space Diversity ◽  
Global Diversity ◽  
Structure Level ◽  
Endocrine Disrupting ◽  
Activity Cliffs

Global diversity and activity landscape analysis of endocrine-disrupting chemicals identifies activity cliffs that are rationalized at the structure level.

scholarly journals Altering rat sexual behavior to teach hormonal regulation of brain imprinting

2019 ◽  
Vol 43 (4) ◽  
pp. 458-466
Author(s):  
Rodney D. Geisert ◽  
Amanda L. Schmelzle ◽  
Michael F. Smith ◽  
Jonathan A. Green
Keyword(s):  
Estrogen Receptor ◽  
Sexual Behavior ◽  
Aromatase Inhibitor ◽  
Receptor Antagonist ◽  
Mating Behavior ◽  
Neonatal Rats ◽  
Female Sexual Behavior ◽  
Ici 182,780 ◽  
Estrogen Receptor Antagonist ◽  
The Brain

In this teaching laboratory, students design and perform an experiment to determine estrogen’s role in imprinting the brain of neonatal rats to express either male or female sexual behavior. A discussion question is provided before the laboratory exercise in which each student is asked to search the literature and provide written answers to questions and to formulate an experiment to test the role of estrogen in imprinting the mating behavior of male and female rats. Students discuss their answers to the questions in laboratory with the instructor and design an experiment to test their hypothesis. In male rats, testosterone is converted by aromatase expressed by neurons in the brain to estrogen. Production of estrogen in the brain of neonatal rats imprints mating behavior in males, where a lack of estrogen action in the brain imprints female sexual behavior. The model involves administering exogenous testosterone to imprint male behavior in female pups or administration of an aromatase inhibitor (letrozole) or an estrogen receptor antagonist (ICI 182,780) to imprint female sexual behavior in male pups. In the model, litters of neonatal pups are treated with either carrier (control), testosterone propionate, aromatase inhibitor (letrozole), or an estrogen receptor antagonist (ICI 182,780) postnatally on days 1 and 3. Alteration of mating behavior is evaluated through the numbers of males and females that breed and establish pregnancy. This is a very simple protocol that provides an excellent experiment for student discussion on the effects of hormone action on imprinting brain sexual behavior.

Increased testicular Sertoli cell population induced by an estrogen receptor antagonist

2013 ◽  
Vol 366 (1) ◽  
pp. 53-58 ◽  
Author(s):  
Trish Berger ◽  
Alan J. Conley ◽  
Monica Van Klompenberg ◽  
Janet F. Roser ◽  
Russell C. Hovey
Keyword(s):  
Estrogen Receptor ◽  
Receptor Antagonist ◽  
Sertoli Cell ◽  
Cell Population ◽  
Estrogen Receptor Antagonist

A new mechanism of estrogen action in prostate cancer: Inhibition of tissue androgen production and prostate cancer growth by Estradiol in androgen independent prostate cancer xenografts

2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 15509-15509
Author(s):  
B. Montgomery ◽  
P. Nelson ◽  
D. L. Hess ◽  
R. Vessella ◽  
E. Corey
Keyword(s):  
Prostate Cancer ◽  
Estrogen Receptor ◽  
Tumor Growth ◽  
Receptor Antagonist ◽  
Human Prostate ◽  
Human Prostate Cancer ◽  
Ici 182,780 ◽  
Estrogen Receptor Antagonist ◽  
Serum Androgens ◽  
Androgen Independent

15509 Background: Estrogens are effective agents in treating prostate cancer in patients in which serum androgens are already at ‘castrate‘ or anorchid levels. The mechanisms whereby estrogens inhibit ‘androgen-independent‘ prostate cancer are unclear. Methods: The androgen-independent human prostate cancer xenograft LuCaP 35V was implanted into orchiectomized male SCID mice and established tumors were treated with placebo pellets, 17β-estradiol (E2) slow-release pellets or E2 with the estrogen receptor antagonist ICI 182,780 as previously described (Clin Cancer Res 8:1003). Effects of E2 on tumor growth and tissue testosterone (T) and dihydrotestosterone (DHT) levels were evaluated by radioimmunoassay. Results: E2 significantly inhibited growth of androgen-independent LuCaP35V ( ∼35% inhibition at 4 weeks, p=0.0047, and increased survival of tumor bearing animals, (p trend =0.03) . The estrogen receptor antagonist ICI 182,780 did not block E2 inhibition of tumor growth, suggesting a receptor independent mechanism of tumor suppression. We then examined the effect of E2 on tissue T and DHT. E2 suppressed levels of tumor T and DHT in treated tumors. Tissue androgens in placebo treated LuCaP35V xenografts were; T=1.21 (± 0.18) pg/mg and DHT=3.54 (±1.07) pg/mg, and in E2-treated LuCaP35V T=0.23 (±0.09) pg/mg and DHT =0.44 (±0.14) pg/mg, (p<0.001). Levels of T and DHT in control liver tissue from both placebo and E2-treated animals were equivalent, at less than 0.2 pg/mg. Conclusions: We have shown that E2 inhibits growth of the androgen- independent human prostate cancer xenograft LuCaP35V, and that this inhibition is estrogen receptor independent. E2 significantly suppressed tumor tissue T and DHT suggesting a new mechanism of E2 mediated growth inhibition of androgen independent prostate cancer, potentially through inhibition of tumoral steroidogenesis. This model of ‘intracrine‘ tumor androgen production can be used to evaluate other inhibitors of tissue steroidogenesis. No significant financial relationships to disclose.

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