Environmental polycyclic aromatic hydrocarbons affect androgen receptor activation in vitro

Vinggaard, Anne Marie; Hnida, Christina; Larsen, John Christian

doi:10.1016/s0300-483x(00)00143-8

Cited by 127 publications

(51 citation statements)

References 24 publications

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“…This observation is significant because it suggests that the reduced sperm motility observed among treated rats is secondary to reduced epididymal exposure to physiological concentrations of androgens. According to Vinggaard et al (2000), Kizu et al (2003), and Charles et al (2005), PAHs including BaP and/or their metabolites perturb the androgen-dependent processes in target tissues by acting as antiandrogens. Benzo(a)pyrene may interrupt epididymal function by competing for androgen receptors in this organ (Mahony and Hodgen, 1995).…”

Section: Discussionmentioning

confidence: 99%

Alteration of fertility endpoints in adult male F-344 rats by subchronic exposure to inhaled benzo(a)pyrene

Ramesh

Inyang

Lunstra

et al. 2008

Experimental and Toxicologic Pathology

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The objective of this study was to evaluate the reproductive risk associated with exposure of adult male Fisher-344 rats to inhaled benzo(a)pyrene (BaP). Rats were assigned randomly to a treatment or control group. Treatment consisted of sub-chronic exposure of rats via inhalation to 75μg BaP/ m 3 , 4 hours daily for 60 days, while control animals were unexposed (UNC). Blood samples were collected immediately after the cessation of exposures (time 0) and subsequently at 24, 48, and 72 hrs, to assess the effect of bioavailable BaP on plasma testosterone and luteinizing hormone (LH) concentrations. Rats were sacrificed after the last blood collection. Testes were harvested, weighed and prepared for histology and morphometric analysis, and cauda epididymides were isolated for the determination of progressive motility and density of stored spermatozoa. BaP exposure reduced testis weight compared with UNC (Mean ± SE; 2.01 ± 0.11 vs. 3.04 ± 0.16 g; P< 0.025), and caused significant reductions in the components of the steroidogenic and spermatogenic compartments of the testis. Progressive motility and mean density of stored spermatozoa were reduced (P< 0.05). Plasma testosterone concentrations were decreased by two-thirds in BaPexposed rats throughout the time periods studied compared with those of their UNC counterparts (P< 0.05), concomitant with increased concentrations of LH in BaP-exposed rats (P< 0.05). These data suggest that sub-chronic exposure to inhaled BaP contribute to reduced testicular and epididymal function in exposed rats.

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Section: Discussionmentioning

confidence: 99%

Alteration of fertility endpoints in adult male F-344 rats by subchronic exposure to inhaled benzo(a)pyrene

Ramesh

Inyang

Lunstra

et al. 2008

Experimental and Toxicologic Pathology

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“…Tyler et al identified 3-phenoxybenzylalcohol, a metabolite of the pyrethroid permethrin, as an antiandrogen in genetically modified yeast cells (Tyler et al 2000). In addition, polycyclic aromatic hydrocarbons block AR activation in vitro (Vinggaard et al 2000) and suppress androgen-dependent growth of accessory sex organs in juvenile male rats (Chang and Liao 1987). Recently, several phenolic chemicals demonstrated antiandrogenic activity in a reporter cell line (Paris et al 2002).…”

mentioning

confidence: 99%

Interlaboratory Comparison of Four in Vitro Assays for Assessing Androgenic and Antiandrogenic Activity of Environmental Chemicals

Körner¹,

Vinggaard²,

Térouanne³

et al. 2004

Environ Health Perspect

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“…On the other hand, reporter-gene assays are available to test androgenicity of chemicals or metabolites [20][21][22][23]. Concerning reporter-gene systems it has to be mentioned that artificially constructed plasmids are far apart from the more complex androgen dependent endogenous gene expression.…”

Section: Discussionmentioning

confidence: 99%

“…In recombinant reporter-gene assays after co-transfection of cells, the ligand-activated receptors initiate transcription of a reporter gene [20][21][22][23], e. g. luciferase. Activity of the reporter gene is directly related to the transcriptional activation by the test compound.…”

Section: Introductionmentioning

confidence: 99%

Characterisation of gene expression patterns in 22RV1 cells for determination of environmental androgenic/antiandrogenic compounds

Hartel

Didier

Pfaffl

et al. 2003

The Journal of Steroid Biochemistry and Molecular Biology

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Alteration of androgen receptor function due to hormonally active compounds in the environment, may be responsible for impaired reproductive function in aquatic wildlife. Based on human prostate carcinoma 22RV1 cells, a cell culture expression system was established to test effects of putative androgenic/antiandrogenic compounds on endogenous gene expression. 22RV1 cells were shown to express human androgen receptor, but not human progestin (hPR) or human oestrogen receptor (hER) ␣ and ␤. Six androgen-regulated genes (ARGs) were chosen to determine androgenic/antiandrogenic action using highly sensitive real-time RT-PCR. Results showed that gene expression is altered in a time-dependent manner. After stimulation of cells by DHT (10 nM), synthetic androgen R1881 (1 nM), or organic pesticides (difenoconazole, fentinacetate, tetramethrin) TMPRSS2 mRNA expression was down-regulated by the factor 0.6 after 24 h of DHT treatment. Similar results were obtained when cells were assayed for mRNA expression of PSA after fentinacetate and R1881 stimulation. In contrast, TMPRSS2 expression was up-regulated by the factor 0.9 when cells were stimulated by tetramethrin. Final goal of the work is a sensitive determination of differential gene expression by different compounds under study, achievement of substance-specific expression patterns and function related analysis of potential androgens/antiandrogens.

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Environmental polycyclic aromatic hydrocarbons affect androgen receptor activation in vitro

Cited by 127 publications

References 24 publications

Alteration of fertility endpoints in adult male F-344 rats by subchronic exposure to inhaled benzo(a)pyrene

Alteration of fertility endpoints in adult male F-344 rats by subchronic exposure to inhaled benzo(a)pyrene

Interlaboratory Comparison of Four in Vitro Assays for Assessing Androgenic and Antiandrogenic Activity of Environmental Chemicals

Characterisation of gene expression patterns in 22RV1 cells for determination of environmental androgenic/antiandrogenic compounds

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