Pronounced induction of testicular PGF(2 alpha) and suppression of testosterone by cadmium-prevention by zinc.
In order to investigate the effects of cadmium (Cd) on testicular prostaglandin F(2 alpha) (PGF(2 alpha)) production, adult male Sprague-Dawley rats were exposed to CdCl(2) by subcutaneous injections. Dose-response as well as temporal-response experiments were performed, and PGF(2 alpha) levels were determined by radioimmunoassay (RIA). The highest cadmium dose (10 micromol/kg) caused a dramatic elevation of testicular PGF(2 alpha), which was established to occur 48 h after exposure. At this point of time, cadmium-treated animals displayed PGF(2 alpha) levels 16.7 times higher than saline-injected controls. No significant differences were found with the lower doses used (1 and 5 micromol/kg). In addition, the influence of pre-treatment with zinc (Zn) was assessed. The very strong stimulatory effect on PGF(2 alpha) synthesis (22.3-fold) detected after exposure to 20 micromol/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 PGF(2 alpha) levels showed drastically lowered concentrations of testosterone. Zinc pre-treatment abolished not only the cadmium-induced rise in PGF(2 alpha) 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 PGF(2 alpha) 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.
Gunnarsson
David
D
Department of Molecular Biology, Umeå University, S-901 87 Umea, Sweden.
Svensson
Mona
M
Selstam
Gunnar
G
Nordberg
Gunnar
G
D000704:Analysis of Variance; D000818:Animals; D019256:Cadmium Chloride / Q000037:antagonists & inhibitors / Q000633:toxicity*; D015237:Dinoprost / Q000096:biosynthesis*; D007985:Leydig Cells / Q000187:drug effects / Q000378:metabolism; D008297:Male; D010750:Phosphoproteins / Q000187:drug effects / Q000378:metabolism; D011863:Radioimmunoassay; D051381:Rats; D017207:Rats, Sprague-Dawley; D013737:Testis / Q000187:drug effects* / Q000378:metabolism; D013739:Testosterone / Q000096:biosynthesis* / Q000097:blood; D015032:Zinc / Q000494:pharmacology*; D000098682:Steroidogenic Acute Regulatory Protein
D010750:Phosphoproteins; D000098682:Steroidogenic Acute Regulatory Protein; D013739:Testosterone; D015237:Dinoprost; D015032:Zinc; D019256:Cadmium Chloride