PubMed · 14563587
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Mathew S Maurer. 2003-10-15. Age: a nonmodifiable risk factor?. https://doi.org/10.1016/s0735-1097(03)01035-0
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The intestinal brush border fructose transporter GLUT5 (SLC2A5) typically appears in rats after weaning is completed. However, precocious consumption of dietary fructose or in vivo perfusion for 4 h of the small intestine with high fructose (HF) specifically stimulates de novo synthesis of GLUT5 mRNA and protein before weaning is completed. Intermediary signals linking the substrate, fructose, to GLUT5 transcription are not known but should also respond to fructose perfusion. Hence, we used microarray hybridization and RT-PCR to identify genes whose expression levels change during HF relative to high-glucose (HG) perfusion. Expression of GLUT5 and NaPi2b, the intestinal Na+-dependent phosphate transporter, dramatically increased and decreased, respectively, with HF perfusion for 4 h. Expression of >20 genes, including two key gluconeogenic enzymes, glucose-6-phosphatase (G6P) and fructose-1,6-bisphosphatase, also increased markedly, along with fructose-2,6-bisphosphatase, an enzyme unique to fructose metabolism and regulating fructose-1,6-bisphosphatase activity. GLUT5 and G6P mRNA abundance, which increased dramatically with HF relative to HG, alpha-methylglucose, and normal Ringer perfusion, may be tightly and specifically linked to changes in intestinal luminal fructose but not glucose concentrations. G6P but not GLUT5 mRNA abundance increased after just 20 min of HF perfusion. This cluster of gluconeogenic enzymes and their common metabolic intermediate fructose-6-phosphate may regulate fructose metabolism and GLUT5 expression in the small intestine.
Zebrafish (Danio rerio) were exposed for 3 weeks to low concentrations of estradiol including environmentally relevant concentrations (5, 25 and 100 ng/l), encompassing either their embryo-larvae (from fertilization to 21 day post-fertilization (dpf)), juvenile (from 21 to 42 dpf) or adult life stages (>200 dpf) with a view to investigating the most sensitive life stage of the zebrafish to 17beta-estradiol (E2). At all sampling points, whole-body vitellogenin concentrations and gonadal development were analyzed in order to investigate the effects of estrogen exposure on these endpoint in the zebrafish. In the adult stage, additional endpoints were measured including secondary sexual characteristics (manifestation of the uro-genital papillae (UGP) in males), gonadal growth (the gonado-somatic index (GSI)) and sex ratio. For all the different life stage exposures, reproductive performance of the F0 generation was assessed (egg production) and survival and development of the F1 embryo-larvae. Exposure to low concentrations of E2 resulted in vitellogenin induction whatever the life stage exposed but these effects were reversible after depuration. The effective concentration for vitellogenin induction in zebrafish early life stages was 100 ng E2/l, and in adult male zebrafish the effective concentration for vitellogenin induction (between 5 and 25 ng/l) was lower than for the early life stage fish. Exposure to E2 prior to (from fertilization to 21 dpf) and during the time of sex differentiation (from 21 to 42 dpf) also caused disruptions in the process of sexual differentiation (resulting in formation of a retrogonadal cavity in presumptive male, germ cell development and leading to a significant change of the sex ratio towards the female sex at the dose of 100 ng E2/l for the fish exposure as embryo-larvae) and altered patterns of egg production in the subsequent adults. Exposure of adult fish to E2 resulted in a modification of the secondary sexual characteristic in males at 25 and 100 ng E2/l as well as a dose-dependent inhibition of egg production. The findings from this study show that the nature and intensity of the reproductive effects of E2 are dependent of the time and concentration of exposures of zebrafish to E2, some of these effects being permanent (effect on the sexual differentiation) while others being reversible (effect on the Vtg induction). This study demonstrated that early life stages of zebrafish are sensitive to low concentrations of E2 and provides relevant data that could be used for the adaptation of existing fish early life stage test for the in vivo testing of estrogenic compounds. The data presented raise further concerns about the effects of steroid estrogens in the environment on fish reproductive health.
This study reports a reduction of ethoxyresorufin-O-deethylase (EROD) activity in large-sized, older Atlantic tomcod (Microgadus tomcod) collected in the St. Lawrence Estuary (Quebec, Canada) and investigates its relationship over a 4-year period to sex, gonadosomatic index (GSI), condition factor (CF) and cytochrome P4501A (CYP1A) mRNA levels. In addition, the concentrations of polychlorinated biphenyls (PCBs) were measured in a subsample of fish. The reduction of EROD activity with age was observed each year in both sexes and was not related to the GSI. A high proportion of large-sized fish, with a body length greater or equal to 225 mm, were emaciated (CF < or = 0.55). A 6-16-fold reduction of EROD activity and a 2-4-fold reduction of CYP1A mRNA levels were observed in large-sized emaciated females compared to small-sized non-emaciated females. Concentrations of PCBs in liver increased from 1000 to 4000 ng/g lipid weight as the hepatic lipid content and the CF decreased. The inter-annual variation of EROD activity was associated with the variation in CF with lowest EROD activity and CF in 1999. When emaciated fish were excluded from the analyses, EROD activity was still lower (2-5-fold) in large compared to small fish and was no longer related to CF. For similar levels of CYP1A mRNA, EROD activity was lower in large compared to small fish. Thus, there was post-transcriptional inhibition of CYP1A activity in large-sized tomcod, indicative of cellular dysfunction. This response may be related to aging, chronic exposure to toxic contaminants or to selective pressures favoring less responsive individuals. This study demonstrates that fish age, size, and CF are important variables to consider in studies using EROD activity as an indicator of environmental contamination. The main finding was that a large part of the reduction of CYP1A with age in St. Lawrence Estuary tomcod was associated with severe emaciation of a large proportion of large-sized fish. Hepatic concentrations of contaminants covaried with the CF and the effects of these two variables on CYP1A could not be discriminated.