Contamination with depleted or enriched uranium differently affects steroidogenesis metabolism in rat
Résumé
Uranium is a naturally occurring heavy metal found in the Earth's crust. It is an alpha-emitter radioactive element from the actinide group that presents both radiotoxicant and chemotoxicant properties. Some studies revealed that uranium could affect the reproductive system. To distinguish chemical versus radiological effects of uranium on the metabolism of the steroids in the testis, rats were contaminated via their drinking water with depleted or enriched uranium. Animals were exposed to radionuclides for 9 months at a dose of 40 mg/L (560 Bq/L for depleted uranium, 1680 Bq/L for enriched uranium). Whereas depleted uranium did not seem to significantly affect the production of testicular steroid hormones in rats, enriched uranium significantly increased the level of circulating testosterone by 2.5-fold. Enriched uranium contamination led to significant increases in the mRNA levels of StAR (Steroidogenic Acute Regulatory protein; 3-fold, p =.001), cyp11a1 (cytochrome P45011a1; 2.2-fold, p <.001), cyp17a1 (cytochrome P45017a1; 2.5-fold, p =.014), cyp19a1 (cytochrome P45019a1; 2.3-fold, p =.021), and 5α -R1 (5α reductase type 1; 2.0-fold, p =.02), whereas depleted uranium contamination induces no changes in the expression of these genes. Moreover, expression levels of the nuclear receptors LXR (Liver X Receptor) and SF-1 (Steroidogenic Factor 1), as well as the transcription factor GATA-4, were modified following enriched uranium contamination. Altogether, these results show for the first time a differential effect among depleted or enriched uranium contamination on testicular steroidogenesis. It appears that the deleterious effects of uranium are mainly due to the radiological activity of the compound. Copyright © American College of Toxicology.
Mots clés
aromatase
cholesterol monooxygenase (side chain cleaving)
cytochrome P450 17
drinking water
liver X receptor
messenger RNA
radioisotope
steroid
steroid 5alpha reductase
steroidogenic acute regulatory protein
steroidogenic factor 1
testosterone
transcription factor GATA 4
uranyl nitrate
animal experiment
animal tissue
article
chemical analysis
controlled study
male
nonhuman
nucleotide sequence
radiation injury
rat
Sprague Dawley rat
steroid metabolism
steroidogenesis
testis
testosterone blood level
water contamination
Animals
Base Sequence
DNA Primers
Environmental Pollutants
Male
Polymerase Chain Reaction
Rats
Sprague-Dawley
Steroids
Transcription Factors
Uranium
Animalia
Rattus