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In vitro bioassays are increasingly applied to detect endocrine disrupting chemicals (EDCs) in environmental waters. Most studies use human nuclear receptor assays, but this raises questions about their relevance for evaluating ecosystem health. The current study aimed to assess species-specific differences in the activation or inhibition of a range of human and zebrafish nuclear receptors by different water extracts. Wastewater and surface water extracts were run in transactivation assays indicative of the estrogen receptor (ER), androgen receptor (AR), glucocorticoid receptor (GR), progesterone receptor (PR), mineralocorticoid receptor (MR), pregnane X receptor (PXR) and peroxisome proliferator-activated receptor gamma (PPARγ). The transactivation assays were complemented with competitive binding assays for human AR, GR, PR and MR. In most cases, both human and zebrafish nuclear receptor activity were detected in the water extracts. Only some species-specific differences in potency and activity were observed. Water extracts were more active in zebrafish PXR compared to human PXR whereas the opposite was observed for PPARγ. Further, all water extracts inhibited zebrafish PR, while only one extract showed weak anti-progestagenic activity for human PR. Due to these observed differences, zebrafish nuclear receptor assays may be preferable over human nuclear receptor assays to assess the potential risks of EDCs to aquatic organisms. However, recognizing issues with availability of zebrafish nuclear receptor assays and the relatively small differences in responsiveness for many of the human and zebrafish nuclear receptors, including the widely studied ER, the current study supports the continued use of human nuclear receptor assays for water quality monitoring.

Vitamin B6 is well-known for its role as a cofactor in many enzymatic reactions and recently, several epidemiological studies have highlighted the importance of this vitamin as a protective agent against various cancers: elevated vitamin B6 plasma levels were associated with a lower risk of colorectal cancer development, for example. In vivo studies have shown that vitamin B6 decreased cell proliferation and enhanced the immune response. At the cellular level, antioxidant, pro-apoptotic and anti-angiogenic effects have been identified. At the molecular level, vitamin B6 is able to inhibit the transactivation potential of various nuclear receptors. Interestingly, a recent paper has described the conjugation of vitamin B6 to RIP140 (receptor interacting protein of 140 kDa), a protein that acts as a transcriptional corepressor of nuclear receptors. This post-translational modification increases the transcriptional repression of RIP140 and regulates its subcellular localization and its ability to interact with different protein partners. Finally, vitamin B6 is involved in the methyl donor cycle ant thus, some of the antitumor properties of vitamin B6 may involve an indirect effect on the level of DNA or histone methylation. All of these mechanistic and clinical data justify further studies to decipher the mechanism of action of vitamin B6 and its clinical interest in combination with molecules typically used in chemotherapy or hormonal therapy.

Resume L’enquete Epipage (1997) a fait etat d’une surmortalite et d’une surmorbidite en Languedoc-Roussillon par rapport aux autres regions de France. Afin de disposer de donnees actualisees, nous avons mis en place un tableau de bord regional de la grande prematurite depuis 2003. Notre objectif etait d’analyser l’evolution de la mortalite et de la morbidite des grands prematures entre 1997 et 2003–2005. Methodes Nous avons analyse la mortalite et la morbidite (respiratoire, neurologique, digestive) des enfants nes vivants entre 22 et 32 SA et admis vivants en neonatologie inclus dans l’enquete Epipage en 1997 et de ceux inclus dans le tableau de bord regional entre 2003 et 2005. Entre ces 2 periodes d’etudes, les pratiques professionnelles ont ete modifiees significativement grâce au travail en reseau. Resultats Nous avons analyse les donnees recueillies chez 3121 enfants de l’etude Epipage et 1111 enfants du tableau de bord regional. Nous avons observe une reduction significative (p Conclusion Nous avons observe une amelioration significative du pronostic des grands prematures concomitante d’une amelioration des pratiques professionnelles consecutive au travail en reseau. Il est important de tenir compte de ces resultats pour faire beneficier d’une information pertinente les professionnels de la perinatalite et donc indirectement les parents.

De nombreuses molecules environnementales agissent comme des perturbateurs endocriniens (PE) pouvant alterer le fonctionnement du systeme hormonal et ainsi avoir des effets nefastes sur la sante humaine. La plupart de ces composes, largement dissemines dans notre environnement, sont des produits de synthese tels que les bisphenols, les phtalates, les parabenes ou encore les pesticides. Les PE ont pour cibles principales les recepteurs nucleaires d’hormones (RN), des facteurs de transcription qui en reponse a la liaison de petites molecules endogenes jouent un role essentiel toutes les fonctions metaboliques et physiologiques chez les metazoaires. Les PE sont ainsi susceptibles de perturber de nombreux processus de regulation et peuvent etre a l’origine de troubles de la reproduction, du metabolisme ou meme de cancers. Dans ce contexte, nous developpons un projet visant a decrire l’action des polluants environnementaux sur les RN a l’echelle moleculaire. Pour cela nous utilisons une combinaison d’approches biochimique, cristallographique, biophysique et cellulaire. Ces differentes approches nous ont permis de mettre en evidence des modes de liaisons originaux des PEs qui peuvent beaucoup differer de ceux des ligands naturels ou pharmaceutiques. Nos etudes devraient ainsi permettre d’orienter la recherche et la synthese de nouveaux composes industriels depourvus de proprietes hormonales.