Abstracts

RATIONALE: In male Wistar rats, VPA has recently been shown to lead to testicular atrophy and reduced spermatogenesis. It is not clear whether this is due to a direct effect on the testis or is secondary to an influence on the gonadotropins. To explore this, we wanted to investigate possible changes in peripheral sex steroid hormones, LH and FSH levels in non-epileptic male Wistar rats. METHODS: Seventy male Wistar rats aged 80 days at the start of the study were divided in 4 groups receiving either VPA mixture 200 mg/kg/dose (n=15) or 400 mg/kg/dose (n=20), LTG 5 mg/kg/dose (n=20) or control solution (n=15), given perorally twice daily for 90 days. RESULTS: Serum concentrations were for VPA 115 and 404 ?mol/l measured 6 h after last dose in low- and high-dose treated animals, respectively, while the LTG concentration was 42.3 ?mol/l. All animals tolerated the treatment without signs of discomfort, except for a 16 % reduction in body weight in animals receiving the highest VPA dose. LH showed a dose-dependent, significant increase after VPA treatment to 170% of control values at the lowest (p=0.042, Kruskall-Wallis test) and 318% at the highest (p=0.0018) VPA dose. A significant, 176% increase in FSH was found after high-dose VPA treatment while testosterone levels decreased insignificantly by 17% in high-dose VPA treated animals. LTG, on the other hand, did not cause any change in testosterone, LH or FSH levels. CONCLUSIONS: VPA, but not LTG, significantly increased LH and FSH levels in non-epileptic male Wistar rats while testosterone levels were unchanged or slightly reduced. The finding might imply a centrally mediated endocrine effect of the drug, although a secondary effect due to the influence from peripheral endocrine organs can not be totally excluded. VPA thus also have a drug specific effect on male endocrine function, in addition to the well-known effects on endocrine functions in females.