Éditeur(s) : HAL CCSD Public Library of Science
Résumé : International audience
BACKGROUND: Studies relating long-term exposure to persistent organochlorine pollutants (POPs) with endocrine activities (endocrine disrupting chemicals) on circulating levels of steroid hormones have been limited to a small number of hormones and reported conflicting results. OBJECTIVE: We examined the relationship between serum concentrations of dehydroepiandrosterone, dehydroepiandrosterone sulphate, androstenedione, androstenediol, testosterone, free and bioavailable testosterone, dihydrotestosterone, estrone, estrone sulphate, estradiol, sex-hormone binding globulin, follicle-stimulating hormone, and luteinizing hormone as a function of level of exposure to three POPs known to interfere with hormone-regulated processes in different way: dichlorodiphenyl dichloroethene (DDE), polychlorinated biphenyl (PCB) congener 153, and chlordecone. METHODS: We collected fasting, morning serum samples from 277 healthy, non obese, middle-aged men from the French West Indies. Steroid hormones were determined by gas chromatography-mass spectrometry, except for dehydroepiandrosterone sulphate, which was determined by immunological assay, as were the concentrations of sex-hormone binding globulin, follicle-stimulating hormone and luteinizing hormone. Associations were assessed by multiple linear regression analysis, controlling for confounding factors, in a backward elimination procedure, in multiple bootstrap samples. RESULTS: DDE exposure was negatively associated to dihydrotestosterone level and positively associated to luteinizing hormone level. PCB 153 was positively associated to androstenedione and estrone levels. No association was found for chlordecone. CONCLUSIONS: These results suggested that the endocrine response pattern, estimated by determining blood levels of steroid hormones, varies depending on the POPs studied, possibly reflecting differences in the modes of action generally attributed to these compounds. It remains to be investigated whether this response pattern is predictive of the subsequent occurrence of disease.
ISSN: 1932-6203

hal-00876025
https://hal.archives-ouvertes.fr/hal-00876025
https://hal.archives-ouvertes.fr/hal-00876025/document
https://hal.archives-ouvertes.fr/hal-00876025/file/Persistent_Organochlorine-accepted.pdf
DOI : 10.1371/journal.pone.0066460

Résumé : En Guadeloupe, la prévalence du diabète est deux fois plus élevée qu'en France hexagonale, avec une prédominance féminine. En dehors des facteurs environnementaux, la vitamine D et certains polymorphismes de gènes impliqués dans son métabolisme seraient associés à un risque de pathologies métaboliques. Les androgènes sont également associés aux anomalies du métabolisme glucidique, soit directement, soit via leur transporteur SHBG (Sex Hormone Binding Protein). Nous avons émis les hypothèses de recherche suivantes: 11 le statut en vitamine D et les polymorphismes des gènes impliqués dans son métabolisme pourraient être associés aux paramètres métaboliques chez des sujets Afro-Caribéens (AC). Ils expliqueraient l'importance des pathologies cardiométaboliques en Guadeloupe. 2/ la SHBG pourrait être associée aux anomalies du métabolisme glucidique, indépendamment des stéroïdes sexuels. Nos travaux sont présentés dans 4 études. Nous avons mis en évidence une prévalence élevée du déficit en vitamine D chez les sujets AC diabétiques de type 2. Nous avons trouvé une association significative entre le statut vitaminique D et le risque cardiométabolique chez ces sujets, mais aussi dans une population de sujets en hémodialyse chronique. Les polymorphismes des gènes impliqués dans le métabolisme de la vitamine D sont aussi associés à ce risque. Chez les sujets dysmétaboliques, une relation entre la SHBG, la graisse intra-hépatique, les hépatokines et les paramètres métaboliques a été mise en évidence, indépendamment des stéroïdes sexuels. En conclusion, la vitamine D et la SHBG pourraient être des marqueurs d'intérêt pour le dépistage des sujets à haut risque cardiométabolique.
In Guadeloupe, the prevalence of diabetes is two times higher than in Metropolitan France, with a female predominance. Apart from environmental factors, vitamin D and polymorphisms of genes involved in vitamin D metabolism would be associated with increased risk of metabolic diseases. Androgens are also associated with abnormal glucose metabolism, directly or through the Sex Hormone Binding Protein (SHBG). Our main hypotheses were: 11 Vitamin D status and polymorphisms of genes involved in its metabolism may be associated with metabolic pammeters in Afro-Caribbean (AC). They could explain the importance of cardiometabolic diseases in Guadeloupe. 2/ SHBG may be associated with abnormal glucose metabolism, independently of sex steroids. Our research is presente
http://www.theses.fr/2012AGUY0536/document

Éditeur(s) : HAL CCSD BioScientifica
Résumé : International audience
BACKGROUND: Differences in circulating steroid hormone levels have been hypothesized to explain ethnic differences in steroid-related diseases. The aim of this study was to determine the serum levels of a wide panel of steroid hormones, both androgens and estrogens, in healthy middle-aged African-Caribbean and European men. DESIGN AND METHODS: Serum steroid hormone levels were determined in men participating in a systematic public health study funded by the French National Health Insurance system. Blood was collected in the morning from 304 healthy African-Caribbean and European men aged between 40 and 69 years. Serum steroids were measured by mass spectrometry-gas chromatography, except for DHEAS and sex hormone-binding globulin, which were determined by RIA. Data were analyzed in 10-year age intervals by analysis of covariance, with adjustment for age, body mass index, waist-to-hip ratio, tobacco and alcohol consumption, and season of sampling. RESULTS: Compared with Europeans, African-Caribbean men presented significantly higher serum levels of measured bioavailable testosterone, 4-androstenedione (4-dione), and estrone (E1) regardless of the age group, of 5-androstenediol (5-diol) in those aged 40-49 and 50-59 years, and of testosterone (TT) and dihydrotestosterone in those aged 40-49 years. In contrast, European men aged 40-69 years showed significantly higher serum levels of DHEA and DHEAS. CONCLUSIONS: Significant differences in serum steroid hormone levels were observed in middle-aged African-Caribbean and European men. Whether such differences could contribute to ethnic differences in disease risk in adult men remains to be investigated. Some steroids, such as bioavailable TT, 4-dione, 5-diol, and E1, deserve particular attention.
ISSN: 0804-4643

hal-00876034
https://hal.archives-ouvertes.fr/hal-00876034
DOI : 10.1530/EJE-11-0551
PUBMED : 21951700

Éditeur(s) : HAL CCSD Elsevier
Résumé : International audience
The effects of some progestins on fish reproduction have been recently reported revealing the hazard of this class of steroidal pharmaceuticals. However, their effects at the central nervous system level have been poorly studied until now. Notwithstanding, progesterone, although still widely considered primarily a sex hormone, is an important agent affecting many central nervous system functions. Herein, we investigated the effects of a large set of synthetic ligands of the nuclear progesterone receptor on the glial-specific expression of the zebrafish brain aromatase (cyp19a1b) using zebrafish mechanism-based assays. Progesterone and 24 progestins were first screened on transgenic cyp19a1b-GFP zebrafish embryos. We showed that progesterone, dydrogesterone, drospirenone and all the progesterone-derived progestins had no effect on GFP expression. Conversely, all progestins derived from 19-nortesterone induced GFP in a concentration-dependent manner with EC50 ranging from the low nM range to hundreds nM. The 19-nortestosterone derived progestins levonorgestrel (LNG) and norethindrone (NET) were further tested in a radial glial cell context using U251-MG cells co-transfected with zebrafish ER subtypes (zfER alpha, zfER beta 1 or zfER beta 2) and cyp19a1b promoter linked to luciferase. Progesterone had no effect on luciferase activity while NET and LNG induced luciferase activity that was blocked by ICI 182,780. Zebrafish-ERs competition assays showed that NET and LNG were unable to bind to ERs, suggesting that the effects of these compounds on cyp19a1b require metabolic activation prior to elicit estrogenic activity. Overall, we demonstrate that 19-nortestosterone derived progestins elicit estrogenic activity by inducing cyp19a1b expression in radial glial cells. Given the crucial role of radial glial cells and neuro-estrogens in early development of brain, the consequences of exposure of fish to these compounds require further investigation.
ISSN: 0041-008X

hal-01366373
https://hal-univ-rennes1.archives-ouvertes.fr/hal-01366373
https://hal-univ-rennes1.archives-ouvertes.fr/hal-01366373/document
https://hal-univ-rennes1.archives-ouvertes.fr/hal-01366373/file/Several%20synthetic%20progestins%20disrupt%20the%20glial%20cell.pdf
DOI : 10.1016/j.taap.2016.05.019

Éditeur(s) : HAL CCSD Public Library of Science
Résumé : International audience
Brain-derived neurotrophic factor (BDNF), a member of the neurotrophin family, has emerged as an active mediator in many essential functions in the central nervous system of mammals. BDNF plays significant roles in neurogenesis, neuronal maturation and/or synaptic plasticity and is involved in cognitive functions such as learning and memory. Despite the vast literature present in mammals, studies devoted to BDNF in the brain of other animal models are scarse. Zebrafish is a teleost fish widely known for developmental genetic studies and is emerging as model for translational neuroscience research. In addition, its brain shows many sites of adult neurogenesis allowing higher regenerative properties after traumatic injuries. To add further knowledge on neurotrophic factors in vertebrate brain models, we decided to determine the distribution of bdnf mRNAs in the larval and adult zebrafish brain and to characterize the phenotype of cells expressing bdnf mRNAs by means of double staining studies. Our results showed that bdnf mRNAs were widely expressed in the brain of 7 days old larvae and throughout the whole brain of mature female and male zebrafish. In adults, bdnf mRNAs were mainly observed in the dorsal telencephalon, preoptic area, dorsal thalamus, posterior tuberculum, hypothalamus, synencephalon, optic tectum and medulla oblongata. By combining immunohistochemistry with in situ hybridization, we showed that bdnf mRNAs were never expressed by radial glial cells or proliferating cells. By contrast, bdnf transcripts were expressed in cells with neuronal phenotype in all brain regions investigated. Our results provide the first demonstration that the brain of zebrafish expresses bdnf mRNAs in neurons and open new fields of research on the role of the BDNF factor in brain mechanisms in normal and brain repairs situations.
ISSN: 1932-6203

hal-01359562
https://hal-univ-rennes1.archives-ouvertes.fr/hal-01359562
DOI : 10.1371/journal.pone.0158057
PUBMED : 27336917