Effects of fluorotelomer alcohol 8:2 FTOH on steroidogenesis in H295R cells: Targeting the cAMP signalling cascade

Liu, Chunsheng; Zhang, Xiaowei; Chang, Hong; Jones, Paul D.; Wiseman, Steve; Naile, Jonathan E.; Hecker, Markus; Giesy, John P.; Zhou, Bingsheng

doi:10.1016/j.taap.2010.06.016

Cited by 39 publications

(19 citation statements)

References 40 publications

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“…Some reports have found that PFCs can increase corticosterone in rodents (Austin et al 2003; Zheng et al 2009). In contrast, other studies have found that PFCs reduce cortisol and corticosterone levels in salmon and human cells (Liu et al 2010; Mortensen et al 2011). …”

Section: Introductionmentioning

confidence: 61%

The Association of Prenatal Exposure to Perfluorinated Chemicals with Glucocorticoid and Androgenic Hormones in Cord Blood Samples: The Hokkaido Study

Goudarzi

Araki

Itoh

et al. 2017

Environ Health Perspect

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Background:Perfluorinated chemicals (PFCs) disrupt cholesterol homeostasis. All steroid hormones are derived from cholesterol, and steroid hormones such as glucocorticoids and androgenic hormones mediate several vital physiologic functions. However, the in utero effects of PFCs exposure on the homeostasis of these steroid hormones are not well understood in humans.Objectives:We examined the relationship between prenatal exposure to perfluorooctane sulfonate (PFOS)/perfluorooctanoate (PFOA) and cord blood levels of glucocorticoid and androgenic hormones.Methods:We conducted a hospital-based birth cohort study between July 2002 and October 2005 in Sapporo, Japan (n = 514). In total, 185 mother–infant pairs were included in the present study. Prenatal PFOS and PFOA levels in maternal serum samples were measured using liquid chromatography–tandem mass spectrometry (LC-MS-MS). Cord blood levels of glucocorticoid (cortisol and cortisone) and androgenic hormones [dehydroepiandrosterone (DHEA) and androstenedione] were also measured in the same way.Results:We found a dose–response relationship of prenatal PFOS, but not PFOA, exposure with glucocorticoid levels after adjusting for potential confounders. Cortisol and cortisone concentrations were –23.98-ng/mL (95% CI: –0.47.12, –11.99; p for trend = 0.006) and –63.21-ng/mL (95% CI: –132.56, –26.72; p for trend < 0.001) lower, respectively, in infants with prenatal PFOS exposure in the fourth quartile compared with those in the first quartile. The highest quartile of prenatal PFOS exposure was positively associated with a 1.33-ng/mL higher DHEA level compared with the lowest quartile (95% CI: 0.17, 1.82; p for trend = 0.017), whereas PFOA showed a negative association with DHEA levels (quartile 4 vs. quartile 1: –1.23 ng/mL, 95% CI: –1.72, –0.25; p for trend = 0.004). We observed no significant association between PFCs and androstenedione levels.Conclusions:Our results indicate that prenatal exposure to PFCs is significantly associated with glucocorticoid and DHEA levels in cord blood.Citation:Goudarzi H, Araki A, Itoh S, Sasaki S, Miyashita C, Mitsui T, Nakazawa H, Nonomura K, Kishi R. 2017. The association of prenatal exposure to perfluorinated chemicals with glucocorticoid and androgenic hormones in cord blood samples: the Hokkaido Study. Environ Health Perspect 125:111–118; http://dx.doi.org/10.1289/EHP142

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Section: Introductionmentioning

confidence: 61%

The Association of Prenatal Exposure to Perfluorinated Chemicals with Glucocorticoid and Androgenic Hormones in Cord Blood Samples: The Hokkaido Study

Goudarzi

Araki

Itoh

et al. 2017

Environ Health Perspect

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“…Fluorotelomer alcohols (FTOHs) are major precursors of PFCAs and other related compounds because FTOHs can ultimately degrade to form PFCAs through atmospheric oxidation Young and Mabury, 2010) and biodegradation (Nilsson et al, 2013;Butt et al, 2014). In addition, 1H,1H,2H,2H-perfluoro-1-octanol (6:2 FTOH) and 1H,1H,2H,2H-perfluoro-1-decanol (8:2 FTOH) have also been found to be estrogenic (Maras et al, 2006;Liu et al, 2010).…”

Section: Introductionmentioning

confidence: 99%

Determination of fluorotelomer alcohols in selected consumer products and preliminary investigation of their fate in the indoor environment

et al. 2015

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“…However, the estrogenic compounds 8:2 fluorotelomer alcohol and 6:2 fluorotelomer alcohol decrease the levels of hormone production and expression of steroidogenic genes by reducing cellular levels of cyclic adenosine monophosphate (cAMP) and inhibiting adenylate cyclase (AC) activity. 28 Such studies have suggested the importance of nonreceptor pathways in the regulation of the endocrine system. 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.…”

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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Effects of fluorotelomer alcohol 8:2 FTOH on steroidogenesis in H295R cells: Targeting the cAMP signalling cascade

Cited by 39 publications

References 40 publications

The Association of Prenatal Exposure to Perfluorinated Chemicals with Glucocorticoid and Androgenic Hormones in Cord Blood Samples: The Hokkaido Study

The Association of Prenatal Exposure to Perfluorinated Chemicals with Glucocorticoid and Androgenic Hormones in Cord Blood Samples: The Hokkaido Study

Determination of fluorotelomer alcohols in selected consumer products and preliminary investigation of their fate in the indoor environment

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

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