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Contamination with Depleted or Enriched Uranium Differently Affects Steroidogenesis Metabolism in Rat

Institute for Radiological Protection and Nuclear Safety, Radiological Protection and Human Health Division, Radiobiology and Epidemiology Department, Laboratory of Experimental Nuclear Toxicology, Fontenay-aux-Roses Cedex, France

Jean-Marc A. Lobaccaro

"LXRs, oxysterols and steroidogenic tissus," UMR Clermont-Université–CNRS 6247–INSERM U931 and Centre de Recherche en Nutrition Humaine d’Auvergne, Aubière Cedex, France

Patrick Gourmelon
Maâmar Souidi

Institute for Radiological Protection and Nuclear Safety, Radiological Protection and Human Health Division, Radiobiology and Epidemiology Department, Laboratory of Experimental Nuclear Toxicology, Fontenay-aux-Roses Cedex, France

Correspondence: Address correspondence to Maâmar Souidi, Institut de radioprotection et de Sûreté Nucléaire, Direction de la Radioprotection de l’Homme, Service de Radiobiologie et d’Epidémiologie, laboratoire de Radiotoxicologie Expérimentale, BP n°17, F-92262 Fontenay-aux Roses Cedex, France. E-mail:maamar.souidi{at}irsn.fr

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 5-R1 (5 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.

Key Words: Chronic Contamination • Cytochrome P450s • Nuclear Receptors • Steroidogenesis • Testis • Uranium

International Journal of Toxicology, Vol. 27, No. 4, 323-328 (2008)
DOI: 10.1080/10915810802367057


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