17β‐Estradiol inhibits testosterone‐induced cell proliferation in HepG2 by modulating the relative ratios of 3 estrogen receptor isoforms to the androgen receptor

Xu, Zhixiang; Liu, Jun; Cao, Jianxin; Zhuang, Yongliang; Pan, Xuejun

doi:10.1002/jcb.27111

Cited by 10 publications

(9 citation statements)

References 33 publications

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“…52,53 Androgens can activate transcription of oncoproteins in viral hepatitis whereas estradiol and estrogen receptors are thought to protect hepatocytes from oxidative stress. 53,54 A sex disparity was not apparent in our report, but the possibility for hormonal factors in HCC epidemiology in dogs is intriguing. The breed and neuter findings should be interpreted cautiously though as utilization of a necropsy control population could have introduced an unknown bias.…”

Section: Discussioncontrasting

confidence: 51%

“…Neuter status might be a risk factor for some malignancies in dogs, and gonadal and related hormones are involved in the pathogenesis of HCC in humans . Androgens can activate transcription of oncoproteins in viral hepatitis whereas estradiol and estrogen receptors are thought to protect hepatocytes from oxidative stress . A sex disparity was not apparent in our report, but the possibility for hormonal factors in HCC epidemiology in dogs is intriguing.…”

Section: Discussionmentioning

confidence: 53%

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Hepatic copper and other trace mineral concentrations in dogs with hepatocellular carcinoma

Harro

Smedley

Buchweitz

et al. 2019

Veterinary Internal Medicne

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Background Hepatocellular carcinoma (HCC) is the most common primary liver tumor in dogs. Abnormalities in hepatic copper, iron, zinc, and selenium concentrations increase risk for HCC development in other species, but trace mineral concentrations have not been evaluated in dogs with HCC. Objectives To investigate hepatic trace mineral concentrations in dogs with HCC. Animals Archived liver specimens from 85 dogs with HCC and 85 control dogs. Methods Retrospective case‐control study. A histopathology database was searched to identify dogs with HCC (test population) and an age‐matched control population. Demographic information was retrieved, and H&E and rhodanine stained slides were reviewed for all cases. Copper, iron, zinc, and selenium concentrations were determined in noncancerous liver tissues (test and control population) and in HCC tissues (test population) using inductively coupled plasma mass spectrometry. Results Hepatic copper concentrations (non‐neoplastic hepatic tissue) were greater in test population dogs (median, IQR; 294.9 μg/g, 233.5‐475.9 μg/g) than in control dogs (202.8 μg/g, 135.0‐295.3 μg/g; P < .001). Hepatic zinc concentrations in test (132.1 μg/g,108.6‐163.2 μg/g) and control dogs (151.5 μg/g, 117.1‐184.5 μg/g) also were different (P = .03). Within test population dogs, all trace mineral concentrations were decreased in the HCC tissue as compared to the non‐neoplastic hepatic tissue (all P < .001). Conclusions and Clinical Importance Hepatic copper accumulation and other abnormalities in hepatic trace mineral concentrations could be involved in the pathogenesis of HCC in some dogs.

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Section: Discussioncontrasting

confidence: 51%

Section: Discussionmentioning

confidence: 53%

Hepatic copper and other trace mineral concentrations in dogs with hepatocellular carcinoma

Harro

Smedley

Buchweitz

et al. 2019

Veterinary Internal Medicne

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“…The HEPES-supplemented Krebs–Henseleit buffer (pH 7.4, KHB) was freshly prepared using HEPES (5.95 g/L), d -glucose (2.0 g/L), magnesium sulfate (0.141 g/L), potassium dihydrogenphosphate (0.16 g/L), potassium chloride (0.35 g/L), sodium chloride (6.9 g/L), calcium chloride dihydrate (0.373 g/L), and sodium bicarbonate (2.1 g/L), followed by adjustment to pH 7.4 with NaOH. The utilized substances within this study were neither found (see Supplementary Materials, Figure S14 ) nor reported [ 31 , 32 , 33 , 34 , 35 ] to be cytotoxic within the utilized concentration range and incubation duration.…”

Section: Methodscontrasting

confidence: 61%

Investigation of Radiotracer Metabolic Stability In Vitro with CYP-Overexpressing Hepatoma Cell Lines

Lemm

Köhler

Wodtke

et al. 2022

Cells

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The characterization of novel radiotracers toward their metabolic stability is an essential part of their development. While in vitro methods such as liver microsome assays or ex vivo blood or tissue samples provide information on overall stability, little or no information is obtained on cytochrome P450 (CYP) enzyme and isoform-specific contribution to the metabolic fate of individual radiotracers. Herein, we investigated recently established CYP-overexpressing hepatoblastoma cell lines (HepG2) for their suitability to study the metabolic stability of radiotracers in general and to gain insight into CYP isoform specificity. Wildtype HepG2 and CYP1A2-, CYP2C19-, and CYP3A4-overexpressing HepG2 cells were incubated with radiotracers, and metabolic turnover was analyzed. The optimized protocol, covering cell seeding in 96-well plates and analysis of supernatant by radio thin-layer-chromatography for higher throughput, was transferred to the evaluation of three 18F-labeled celecoxib-derived cyclooxygenase-2 inhibitors (coxibs). These investigations revealed time-dependent degradation of the intact radiotracers, as well as CYP isoform- and substrate-specific differences in their metabolic profiles. HepG2 CYP2C19 proved to be the cell line showing the highest metabolic turnover for each radiotracer studied here. Comparison with human and murine liver microsome assays showed good agreement with the human metabolite profile obtained by the HepG2 cell lines. Therefore, CYP-overexpressing HepG2 cells provide a good complement for assessing the metabolic stability of radiotracers and allow the analysis of the CYP isoform-specific contribution to the overall radiotracer metabolism.

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“…ERα36, which is a membrane variant of ERα, is also affected by the dysregulation of estrogen signaling (32). ERα has been demonstrated to suppress the activity of ERα36 promoter in an estrogen-independent manner (33).…”

Section: Discussionmentioning

confidence: 99%

The effects of estradiol on inflammatory and endothelial dysfunction in rats with preeclampsia

Lin¹,

Jin²,

Shan³

2020

Int J Mol Med

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Preeclampsia (PE), a hypertensive disorder during pregnancy, has adverse effects to both the mother and the fetus. Maternal inflammatory and vascular endothelial dysfunction are important factors in the pathogenesis of PE. The present study aimed to investigate the effects of estradiol (E2) on inflammatory and endothelial dysfunction in an N (omega)-nitro-L-arginine methyl ester (L-NAME)-induced rat model of PE. Adult pregnant female Sprague-dawley rats were divided into four equal groups between days 7 and 11 of gestation and treated as follows: i) Pregnant rats receiving daily intraperitoneal (i.p.) injections of equal volume of 0.9% normal saline (NS) (control group, n=12); ii) pregnant rats receiving daily i.p. injections of L-NAME at 50 mg/kg (L-NAME group, n=12); iii) pregnant rats receiving a daily i.p. injection of 50 mg/kg L-NAME and NS from day 11 (L-NAME + NS group, n=12); and iv) pregnant rats receiving daily i.p. injections of 50 mg/kg L-NAME and 100 µg/kg/day E2 from day 11 (L-NAME + E2 group, n=12). On day 21, blood pressure (BP) and the level of 24-h urine protein in the maternal rats, fetal weight and percentage of stillbirths following a cesarean section were recorded. The activities of nitric oxide (NO) and inducible NO synthase (iNOS), the levels of inflammatory cytokines [interleukin (IL)-1β, IL-6, interferon-γ and monocyte chemoattractant protein-1], adherence factors (cd49d, intracellular adhesion molecule 1 and lymphocyte function-associated antigen-1) and uterine angiogenic status (Fms-like tyrosine kinase-1, vascular cell adhesion molecule and matrix metalloproteinase 2/9) were also assessed. In addition, the histopathology of the placenta, the expression of estrogen receptor α 36 (ERα36), ERα, ERβ and G protein-coupled ER, as well as the activation of the toll-like receptor 4 (TLR4) signaling pathway (TLR4, myeloid differentiation primary response 88, IL-1 receptor-associated kinase 4 and tumor necrosis factor receptor-associated factor 6) were evaluated by H&E staining, immunofluorescence and western blot assays. Treatment with L-NAME increased the BP, urine protein and rate of stillbirths and suppressed fetal weight compared with those in the control group. The L-NAME-induced effects were attenuated by the administration of E2. In addition, the administration of E2 decreased inflammation and NO levels and altered the uterine angiogenic status. The histological analysis of PE rat placenta in the E2-treated group confirmed the effects on biochemical parameters. Of note, E2 treatment significantly suppressed the TLR4 signaling pathway. In the rat model of PE, adverse outcomes including BP, fetal rat weight and proteinuria, high neonatal death rate, inflammatory response, oxidative stress and endothelial dysfunction were attenuated by exogenous E2 administration, which may present a novel approach for the clinical treatment of PE.

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17β‐Estradiol inhibits testosterone‐induced cell proliferation in HepG2 by modulating the relative ratios of 3 estrogen receptor isoforms to the androgen receptor

Cited by 10 publications

References 33 publications

Hepatic copper and other trace mineral concentrations in dogs with hepatocellular carcinoma

Hepatic copper and other trace mineral concentrations in dogs with hepatocellular carcinoma

Investigation of Radiotracer Metabolic Stability In Vitro with CYP-Overexpressing Hepatoma Cell Lines

The effects of estradiol on inflammatory and endothelial dysfunction in rats with preeclampsia

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