Stéroïde | EPFL Graph Search

Les stéroïdes sont un groupe de lipides dérivant de triterpénoïdes (lipides à 30 atomes de carbone), majoritairement le squalène. Ils se caractérisent par un noyau cyclopentanophénanthrénique (stérane) hydrophobe partiellement ou totalement hydrogéné. Habituellement, les carbones C10, C13 sont liés à un groupe méthyle -CH3 et le carbone C17 à un groupe alkyle. Par extension, les stéroïdes incluent également les lipides dont le noyau cyclopentanophénanthrénique a été modifié par scission d'une liaison et l'ajout ou la délétion d'un carbone. En médecine le terme de « stéroïde » peut faire référence aux hormones stéroïdiennes ou aux stéroïdes neuroactifs. Dans un contexte sportif, « stéroïde » est habituellement employé pour désigner les stéroïdes anabolisants. Nomenclature et Classification Classification des lipides#Classe des stérols Les différentes instances scientifiques ne s'accordent pas sur la classification. Dans la classification de l'IUPAC, les stéroïdes sont

Detection of environmental glucocorticoids and investigation of their effects using the zebrafish embryo as a model

Anita Orsolya Hidasi

Synthetic glucocorticoids (GCs) are widely used anti-inflammatory drugs. They mimic cortisol, the natural stress hormone in humans and in fish. Cortisol binds and activates the glucocorticoid receptor (GR), which regulates genes governing development, immune response, osmoregulation, and behavior. Therefore, the presence of GCs in the aquatic environment may cause endocrine disruption through impairing these essential physiological processes in fish. The aim of this thesis was to assess the effects of environmentally relevant concentrations of GCs in teleost fish, focusing on the inflammatory response and molecular mechanisms of GC action on different levels, from mRNA to proteins to metabolites. To confirm the environmental presence of GCs, GC activity was determined along a Swiss freshwater stream impacted by a wastewater treatment plant, using effect-directed analysis. The effluent samples showed the highest potency to activate the GR, as determined by the GR-CALUX® assay. The chemical analysis found clobetasol propionate (CP), a highly potent GC, to be responsible for 63% of the total GR activity in the sample. CP was selected as a model chemical to study GC effects in fish. Embryos of zebrafish (Danio rerio) aged until 5 days post fertilization (dpf) were used as a model organism; working with embryonic stages is a refinement of animal experiments. We demonstrated that CP is readily taken up by the embryos. Bacterial lipopolysaccharides (LPS) induce one of the main inflammatory cascades. As observed in LPS challenge assays, the inflammatory response of the embryos was significantly reduced after exposure to ¿0.1 nM CP. We showed that mRNA expression of several LPS mechanism- and GC action-related genes was regulated by CP. Among them, Annexin a1b (anxa1b) was significantly down-regulated after exposure to ¿0.05 nM CP. Sensitive regulation of anxa1b by the non-steroidal anti-inflammatory drug diclofenac (DCF) suggested that this gene product is a potential biomarker of steroidal and non-steroidal immunosuppressive effects. An LC-MS/MS-based targeted proteomics technique was developed to measure proteins, as it is these molecules that actually carry out cellular functions. 12 out of 40 GC action-related protein targets were detectable in control embryo digests and were subsequently monitored after CP, DCF and grab water sample exposures. We found that the muscle protein Myhz2 was regulated only after DCF exposure, while I¿B¿, an anti-inflammatory protein, was regulated only by CP, in agreement with mRNA level data. Global and targeted metabolomics analyses were performed in zebrafish embryos exposed to CP from 4 to 5 dpf, in collaboration with M. Lamoree (VU Amsterdam). Several of the detected compounds showed significant response to CP: lysine, nicotinamide, choline, hypoxanthine, tyrosine and tryptophan. To conclude, this thesis demonstrates that GCs are present in the aquatic environment and may suppress the inflammatory response of fish at environmentally relevant concentrations.

EPFL2016

Biogeography and biochemistry of bile acid 7-dehydroxylation in the mammalian gut

Solenne Anne Marie Marion

Bile acids (BAs) are small molecules synthesized by the host and chemically modified by the microorganisms inhabiting the intestinal tract. The microbial transformation of BAs in the gut is critical to BA-mediated signaling as it modifies their amount and affinity for specific BA receptors. Bile acid 7-dehydroxylating bacteria are intestinal commensals of particular importance as they catalyze the dehydroxylation of liver-derived (primary) bile acids at the C7 position (i.e., 7-dehydroxylation) and produce secondary bile acids. One of the major receptors for secondary BAs is Takeda G-protein receptor 5 (TGR5), and it is associated with regulation of energy expenditure and glucose management, protection from liver steatosis and inflammation. In addition, 7-dehydroxylated bile acids are also associated with protection from infection by specific intestinal pathogens (i.e., Clostridioides difficile). Thus, through their action on primary BAs, 7-dehydroxylating (7-DH-ing) bacteria play an important role in health promotion and in the functioning of major physiological processes in the body such as insulin secretion, thermogenesis and immune responses. Despite these potentially important roles in the mammalian host, bile acid 7-dehydroxylating bacteria are poorly studied and much remains to be deciphered regarding their metabolism, diversity, abundance in the gut, and colonization dynamics in the host. Here, we use Clostridium scindens, as model organism to study bile acid 7-dehydroxylation in vitro and in gnotobiotic mice. We found that C. scindens metabolize only human primary bile acids (CA and CDCA). We uncovered the formation of a novel intermediate during CA 7-dehydroxylation by C. scindens in vitro: 12-oxoLCA. In vivo, using NanoSIMS and metabolomic analysis, we demonstrated that the large intestine constitutes C. scindens primary ecological niche in gnotobiotic mice. Following up on the discovery of the 12oxoLCA, we hypothesized the existence of another 7-dehydroxylation pathway for cholic acid. We postulated that it may involve the B and C rings of the steroid structure and may entail the oxidation/reduction of the C12- hydroxyl group. Thus, it was dubbed the putative vertical pathway. Conducting in vitro enzymatic assays with purified enzymes, we confirmed the existence of this novel vertical biosynthetic 7-dehydroxylation pathway for cholic acid, the most abundant primary bile acid in humans, and identified the core of enzymes necessary and sufficient for CA 7-dehydroxylation. Furthermore, we used a coupled metabolomic and metaproteomic approach to probe in vivo activity of the gut microbial community in a gnotobiotic mouse model. Additionnally, we also considered the bile acid profile in mice with more complex microbiota or with no microbiota. By comparing the bile acid profile of the different mice models along with expression of key genes of bile acid synthesis, we emphasized the profound influence of the gut microbial community on BA pool homeostasis. Altogether, our data provides a significant contribution to our collective understanding of the microbiology of bile acid 7-dehydroxylating bacteria, a group of gut commensals highly relevant to host health but that remains poorly characterized. The discovery of a novel 7-dehydroxylation pathway is a major scientific achievement of this thesis.

EPFL2020

No Scope for Social Modulation of Steroid Levels in a Year-Round Territorial Damselfish

Katarina Damjanovic

Both latitude and mating system have been proposed to shape relationships between steroid hormone levels and social behavior. Recently it has been postulated that species with long lasting non-seasonal territorial behavior have low androgen responsiveness. Tropical damselfishes are an ideal family to test this proposition because they show a large variety in mating systems. Here we contribute to the comparative dataset by measuring the response in steroid levels after social modulation in the banded sergeant, Abudefduf septemfasciatus, a species with non-seasonal territoriality. In highly territorial and brooding males, we found low androgen and cortisol levels that did not increase after experimental intraspecific simulated territorial intrusions (STI tests). No relationship was found between the variation in steroid hormone levels and territorial responses to naturally occurring territorial intrusions. Although steroid levels were low, male A. septemfasciatus were highly territorial both to STI challenges and to fishes that passed the territory. They often chased intruders for several meters away from the territory. This indicates that during nest defence in a non-seasonal territorial damselfish species, territorial behaviors are shown independent of variation in androgen and cortisol levels. J. Exp. Zool. 323A: 80-88, 2015. (c) 2014 Wiley Periodicals, Inc.

Wiley-Blackwell2015