In vivo and in vitro effects of PCB126 and PCB153 on rat testicular androgenesis

Andrić, Nebojša; Kostic, Tatjana S.; Kaišarević, Sonja; Fa, Svetlana; Pogrmić, Kristina; Kovačević, Radmila

doi:10.1016/j.etap.2007.10.002

Cited by 7 publications

(4 citation statements)

References 23 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Experiments were performed 24–48 h after dispersion. Isolation and purification of Leydig cells was performed as previously described (Andric et al, 2008, Pogrmic-Majkic et al, 2010), and experiments were performed 3–4 h after dispersion.…”

Section: Methodsmentioning

confidence: 99%

“…Procedure of isolation and purification of Leydig cells is published previously (Andric et al, 2008; Pogrmic et al, 2009). Cells were allowed 3 h to attach to 24-well plates (2.5×10 5 cells/0.5 ml culture medium/well) and then cultured in M199–0.1% BSA with a low subsaturated dose of hCG (0.25 ng/ml) for 2 h in the absence or presence of different concentrations of atrazine, 1 mM IBMX, and/or forskolin in 0.1 or 1 µM concentration.…”

Section: Methodsmentioning

confidence: 99%

See 1 more Smart Citation

Atrazine acts as an endocrine disrupter by inhibiting cAMP-specific phosphodiesterase-4

Kučka

Pogrmić-Majkić

et al. 2012

Toxicology and Applied Pharmacology

111

View full text Add to dashboard Cite

Atrazine, one of the most commonly used herbicides worldwide, acts as an endocrine disruptor, but the mechanism of its action has not been characterized. In this study, we show that atrazine rapidly increases cAMP levels in cultured rat pituitary and testicular Leydig cells in a concentration-dependent manner, but less effectively than 3-isobutyl-1-methylxanthine, a competitive non-specific inhibitor of phosphodiesterases (PDEs). In forskolin (an activator of adenylyl cyclase)- and probenecid (an inhibitor of cyclic nucleotide transporters)-treated cells, but not in 3-isobutyl-1-methylxanthine-treated cells, atrazine further increased cAMP levels, indicating that inhibition of PDEs accounts for accumulation of cAMP. In contrast to cAMP, atrazine did not alter cGMP levels, further indicating that it inhibits cAMP-specific PDEs. Atrazine-induced changes in cAMP levels were sufficient to stimulate prolactin release in pituitary cells and androgen production in Leydig cells, indicating that it acts as an endocrine disrupter both in cells that secrete by exocytosis of prestored hormones and in cells that secrete by de novo hormone synthesis. Rolipram abolished the stimulatory effect of atrazine on cAMP release in both cell types, suggesting that it acts as an inhibitor of PDE4s, isoforms whose mRNA transcripts dominate in pituitary and Leydig cells together with mRNA for PDE8A. In contrast, immortalized lacto-somatotrophs showed low expression of these mRNA transcripts and several fold higher cAMP levels compared to normal pituitary cells, and atrazine was unable to further increase cAMP levels. These results indicate that atrazine acts as a general endocrine disrupter by inhibiting cAMP-specific PDE4s.

show abstract

Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Atrazine acts as an endocrine disrupter by inhibiting cAMP-specific phosphodiesterase-4

Kučka

Pogrmić-Majkić

et al. 2012

Toxicology and Applied Pharmacology

111

View full text Add to dashboard Cite

show abstract

“…Experiments were approved by the Ethics Committee for Protection and Welfare of Experimental Animals at University of Novi Sad and conducted in accordance with the statements of National Law for Animal Welfare (copyright March 2009). Isolation and purification of Leydig cells was performed as previously described (Andric et al, 2008, Pogrmic-Majkic et al, 2010). Leydig cells were seeded in 24-well plates (250000 cells/500 μl DMEM/F12 /well and allowed 3 h to attach before applying HBCDD for 6 h at doses: 0, 1, 2, 5 and 10 μM in the absence (basal) and presence of hCG (0.125, 0.25, 1 and 10 ng/ml).…”

Section: Methodsmentioning

confidence: 99%

Acute effects of hexabromocyclododecane on Leydig cell cyclic nucleotide signaling and steroidogenesis in vitro

Pogrmić-Majkić

Dakic

et al. 2013

Toxicology Letters

View full text Add to dashboard Cite

Hexabromocyclododecane (HBCDD), an additive brominated flame retardant routinely added to various consumer products, was reported to have toxic effects upon biota, including endocrine disruption. In this study, the potential toxicity of HBCDD was tested in peripubertal rat Leydig cells in vitro during 6 h exposure. HBCDD inhibited human chorionic gonadotropin- and forskolin-supported cAMP accumulation and steroidogenesis. It also inhibited basal cAMP production, but elevated basal steroidogenesis. The expression of several cAMP-dependent genes, including steroidogenic acute regulatory protein, cholesterol side chain cleavage enzyme, and 3β-hydroxysteroid dehydrogenase, was also inhibited by HBCDD treatment. Nevertheless, this was not accompanied by a decrease in steroidogenic acute regulatory protein expression, as documented by western blot analysis, and activity of steroidogenic enzymes, as documented by unaffected steroidogenesis in the presence of permeable 22(R)-hydroxycholesterol. However, HBCDD caused significant decrease in mitochondrial membrane potential in untreated and human chorionic gonadotropin-treated cells. This indicates that HBCDD acute toxicity in Leydig cells reflects changes in mitochondrial membrane potential-dependent cAMP production and basal and cAMP-regulated cholesterol transport. This in turn facilitates basal but inhibits cAMP-dependent steroidogenesis. Acute effects of HBCDD treatment on transcription are also indicative of its sustained effects on Leydig cell function.

show abstract

“…Relying on years of high-quality research in the field of animal physiology, specifically in reproductive endocrinology e.g. [1][2][3][4][5][6][7][8][9], the activities of LECOTOX researchers were (and still are) focused on toxic impact of persistent organic pollutants (POPs) on biota with special emphasis on specific sublethal types of toxicity -endocrine disruption, reproductive toxicity, and "dioxin-like" toxicity [10][11][12][13][14][15][16]. Bio analyses based on molecular and cellular biomarkers of effects, such as cytochrome P450 (CYP) enzyme induction and parameters and markers of oxidative stress and early intoxication have been applied in assessment of freshwater ecosystems e.g.…”

mentioning

confidence: 99%

REP-LECOTOX: an example of FP 6 INCO project to strengthen ecotoxicological research in WBC (Western Balkan countries)

et al. 2011

View full text Add to dashboard Cite

FP6 (2007FP6 ( -2009) presented a crucial milestone for LECOTOX, both in terms of overall research performance and its visibility and presentation to international scientific community. The project enabled upgrading and renewal of S&T equipment, hiring new young researchers to reinforce human resources and it facilitated extensive networking -via workshops, exchange of scientific personnel and trainings of young scientists in some of the finest research institutions in the EU in the field of environmental research: Helmholtz Centre for Environmental Research -UFZ, Leipzig, Germany; School of Bioscience, University of Birmingham, UK and RECETOX, Masaryk University, Brno, Czech Republic. The project enabled LECOTOX, focusing mainly on two research topics, i.e. endocrine disruption/ reproductive toxicity, and identification and characterisation of aquatic toxicity, to form a functional competitive research team ready for combining transcriptomics with the established conventional toxicity tests and traditional function-based biomarkers. LECOTOX became well-equipped and experienced research group confident enough to join any FP or otherwise funded ecotoxicological research project and network.

show abstract

In vivo and in vitro effects of PCB126 and PCB153 on rat testicular androgenesis

Cited by 7 publications

References 23 publications

Atrazine acts as an endocrine disrupter by inhibiting cAMP-specific phosphodiesterase-4

Atrazine acts as an endocrine disrupter by inhibiting cAMP-specific phosphodiesterase-4

Acute effects of hexabromocyclododecane on Leydig cell cyclic nucleotide signaling and steroidogenesis in vitro

REP-LECOTOX: an example of FP 6 INCO project to strengthen ecotoxicological research in WBC (Western Balkan countries)

Contact Info

Product

Resources

About