Pronounced induction of testicular PGF2alpha and suppression of testosterone by cadmium: prevention by zinc
2004 (English)In: Toxicology, ISSN 0300-483X, Vol. 200, no 1, 49-58 p.Article in journal (Refereed) Published
In order to investigate the effects of cadmium (Cd) on testicular prostaglandin F2α (PGF2α) production, adult male Sprague–Dawley rats were exposed to CdCl2 by subcutaneous injections. Dose–response as well as temporal–response experiments were performed, and PGF2α levels were determined by radioimmunoassay (RIA). The highest cadmium dose (10 μmol/kg) caused a dramatic elevation of testicular PGF2α, which was established to occur 48 h after exposure. At this point of time, cadmium-treated animals displayed PGF2α levels 16.7 times higher than saline-injected controls. No significant differences were found with the lower doses used (1 and 5 μmol/kg). In addition, the influence of pre-treatment with zinc (Zn) was assessed. The very strong stimulatory effect on PGF2α synthesis (22.3-fold) detected after exposure to 20 μmol/kg cadmium, was completely absent in the group given zinc (1 mmol/kg) prior to cadmium exposure. Plasma testosterone concentrations were determined in the three experiments, and all groups with strongly elevated PGF2α levels showed drastically lowered concentrations of testosterone. Zinc pre-treatment abolished not only the cadmium-induced rise in PGF2α but also the testosterone reduction. Additionally, cadmium was found to inhibit the expression of steroidogenic acute regulatory protein (StAR), which is responsible for the rate-limiting step in steroidogenesis. The present findings establish that cadmium can cause a strong induction of testicular PGF2α production, which might help to explain the well-known antisteroidogenic effect of this heavy metal. Such an inhibitory effect could be due to reduced levels of StAR.
Place, publisher, year, edition, pages
2004. Vol. 200, no 1, 49-58 p.
Cadmium; Rat; Prostaglandin F2α (PGF2α); Steroidogenic acute regulatory protein (StAR); Testis; Testosterone
IdentifiersURN: urn:nbn:se:umu:diva-3525DOI: 10.1016/j.tox.2004.03.003OAI: oai:DiVA.org:umu-3525DiVA: diva2:142271