CONICET | Buscador de Institutos y Recursos Humanos

We studied the mechanism through which intoxication of Wistar rats with dimethoate (D) (1/50 DL50, i.p., three times a week for 5 weeks) inhibits testosterone (T) biosynthesis. Expression of COX-2 was increnented by 44% over control data in Leydig cell suspension from intoxicated rats, while transcription of StAR protein was decreased by 45 to 52 % and the expression of the protein was diminished by 36 to 41 % compared to controls values. F2a and E2 prostaglandins were incremented by 61 to 78% respectively after D intoxication. T level decreased 49% in cellular homogenates. Concomitantly, plasma concentration of LH and FSH were increased. Arachidonate content in Leydig phospholipids decreased by 28% and the docosapolyenoic acids (n3 and n6 series) were diminished by 19 to 30%. Protein carbonyls and ROOHs were increased whereas total antioxidant capacity (FRAP) of sonicated Leydig cells decreased under D treatment. Stimulation of Leydig cells with h-CG (10 nM, overnight) failed to overcome the inhibition caused by D on T production. In conclusion, we demonstrated that decreased T biosynthesis cased by D may be the consequence of (i) inhibition of StAR biological activity due to stimulation of COX-2 and over production of PGF2a, (ii) decreased stimulatory effect of arachidonate on StAR with subsequent alteration in the availability of cholesterol for androgenic pathway, (iii) inhibition of steroidogenic enzymes by direct oxidative injury or indirectly by damage due to a slower transcriptional rate caused by elevated PG2a levels. However, other factors such as alterations in phospholipase A2, ACS4 or Acot2 activity should not be ruled out.