The H295R system for evaluation of endocrine-disrupting effects

Gracia, Tannia; Hilscherová, Klára; Jones, Paul D.; Newsted, John L.; Zhang, Xiaowei; Hecker, Markus; Higley, Eric; Sanderson, J. Thomas; Yu, Richard Man Kit; Wu, Rudolf S.S.; Giesy, John P.

doi:10.1016/j.ecoenv.2006.06.012

Cited by 87 publications

(51 citation statements)

References 38 publications

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“…We exposed H295R cells to different concentrations of TBC in the absence or presence of 10 lM forskolin for 72 h, and then the concentrations of two steroid hormones, E2 and T, in the culture medium supernatant and the relative expression level of nine steroidogenic-related genes (StAR, 3bHSD2, CYP17, CYP21, CYP19, HMGR, 17bHSD1, 17bHSD4 and CYP11A) were measured. Our results showed that forskolin treatment of the H295R cells resulted in more hormone secretion and a generally increase expression of steroidogenic-related genes, which confirms its capability for inducing steroidogenesis in H295R cells and is consistent with previous reports (Gracia et al 2006;Hecker et al 2006). Additionally, TBC exposure caused significantly decrease in steroid hormones in H295R cells.…”

Section: Discussionsupporting

confidence: 81%

“…H295R cells can produce all of the steroid hormones in three different regions of human adrenal cortex and are capable of expressing the key enzyme (aromatase) in the process of steroid synthesis (Wang and Rainey 2012). The H295R steroidogenesis assay has been approved by the Environmental Protection Agency for assessing effects of chemical agents on steroidogenesis (Gracia et al 2006). Besides, the H295R cells treated with synthetic cAMP analogues or activation of adenylate cyclase by forskolin could make the steroidogenic transcript patterns similar to those in normal human adrenal cells, suggesting that the H295R cell line can serve as a good model to assess the risk of adrenocortical toxicity (Cobb et al 1996;Li et al 2013;Oskarsson et al 2006).…”

Section: Introductionmentioning

confidence: 99%

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Effects of tris(2,3-dibromopropyl) isocyanurate on steroidogenesis in H295R cells

Pan

Wang

et al. 2016

Environ Earth Sci

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Tris(2,3-dibromopropyl) isocyanurate (TBC) is widely used in polymer products. It is ubiquitously found in environmental matrices. Previous studies have shown that TBC has potential endocrine-disrupting effects on aquatic organisms. However, the effects on adrenocortical function and the underlying mechanisms are not well characterized. In present study, the H295R cell line was employed to investigate the potential endocrine-disrupting action of TBC. TBC inhibited basal and forskolin-induced sex hormone production but did not exhibit cytotoxicity. The expression of the steroidogenic genes, StAR, 3bHSD2, CYP17, CYP21, CYP19, HMGR, 17bHSD1, 17bHSD4 and CYP11A, was not changed upon TBC exposure. However, the cAMP inducer forskolin strongly induced the expression of all these genes, except for HMGR, 17bHSD1 and 17bHSD4. TBC blocked forskolin-induced StAR, 3bHSD2, CYP17, CYP21 and CYP19 mRNA expression. Our results indicate that TBC can inhibit sex hormone biosynthesis due to the interference with steroidogenic gene transcription in activated condition.

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Section: Discussionsupporting

confidence: 81%

Section: Introductionmentioning

confidence: 99%

Effects of tris(2,3-dibromopropyl) isocyanurate on steroidogenesis in H295R cells

Pan

Wang

et al. 2016

Environ Earth Sci

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“…Primer sequences for genes in this study have been described previously (Table S2 of the Supporting Information). 21 The thermal cycle was 2 min at 95°C followed by 45 cycles of 15 s at 95°C…”

Section: ■ Materials and Methodsmentioning

confidence: 99%

“…Also, this in vitro-based method has been confirmed for the study of the effects of endocrine disruption and validated by the Organization for Economic Co-operation and Development to replace testis explant assays using rodents. 21,29 Here, we studied the effects of PFOI on expression of all steroidogenic genes and production of four hormones to ascertain the modulation of steroidogenesis and endocrinedisrupting effects of PFOI. To investigate the potential toxicity mechanisms of steroidogenesis, cAMP levels and AC activity were examined to elucidate the steroidogenic pathway.…”

Section: ■ Introductionmentioning

confidence: 99%

Perfluorooctyl Iodide Stimulates Steroidogenesis in H295R Cells via a Cyclic Adenosine Monophosphate Signaling Pathway

Wang

Ruan

Liu

et al. 2015

Chem. Res. Toxicol.

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Perfluorinated iodine alkanes (PFIs) are used widely in the organic fluorine industry. Increased production of PFIs has caused environmental health concerns. To evaluate the potential endocrine-disrupting effect of PFIs, we investigated the effects of perfluorooctyl iodide (PFOI) on steroidogenesis in human adrenocortical carcinoma cells (H295R). Levels of aldosterone, cortisol, 17β-estradiol, and testosterone were measured in H295R culture medium upon treatment with perfluorooctanoic acid (PFOA) and PFIs. Expression of 10 steroidogenic genes (StAR, HMGR, CYP11A1, 3βHSD2, 17βHSD, CYP17, CYP21, CYP11B1, CYP11B2, and CYP19) was measured by real-time polymerase chain reaction. Levels of cyclic adenosine monophosphate (cAMP) and adenylate cyclase (AC) activity were measured to understand the underlying mechanism of steroidogenic perturbations. Levels of production of aldosterone, cortisol, and 17β-estradiol were elevated significantly, and the level of testosterone generation decreased upon treatment with 100 μM PFOI. Similar to the effect induced by forskolin (AC activator), expression of all 10 genes involved in the synthesis of steroid hormones was upregulated significantly upon exposure to 100 μM PFOI. PFOA had no effect on steroid hormone production or steroidogenic gene expression even though it is highly structurally similar with PFOI. Therefore, the terminal -CF 2 I group in PFOI could be a critical factor for mediation of steroidogenesis. PFOI increased AC activity and cAMP levels in H295R cells, which implied an underlying mechanism for the disturbance of steroidogenesis. These data suggest that PFOI may act as an AC activator, thereby stimulating steroidogenesis by activating a cAMP signaling pathway.

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“…In the latter case, chemicals can alter steroidogenic gene expression or enzyme activities and have the potential to alter concentrations of hormones in blood and tissues (Hilscherova et al, 2004). In this regard, the utility of in vitro assay systems, the human adrenocortical carcinoma cells (H295R), has been developed for rapid screening of endocrine disrupting potencies of chemicals or toxicants and identification of novel mechanisms of endocrine disruption (Sanderson et al, 2000;Gracia et al, 2006). H295R cells maintain physiological characteristics of zonally undifferentiated fetal adrenal cells and express all genes involved in steroidogenesis (Fig.…”

Section: Introductionmentioning

confidence: 99%

The H295R system for evaluation of endocrine-disrupting effects

Cited by 87 publications

References 38 publications

Effects of tris(2,3-dibromopropyl) isocyanurate on steroidogenesis in H295R cells

Effects of tris(2,3-dibromopropyl) isocyanurate on steroidogenesis in H295R cells

Perfluorooctyl Iodide Stimulates Steroidogenesis in H295R Cells via a Cyclic Adenosine Monophosphate Signaling Pathway

Modulation of steroidogenic gene expression and hormone synthesis in H295R cells exposed to PCP and TCP

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