Our previous results show that leptin, as well as nitric oxide (NO) and some antioxidants (histidine dipeptides - HDP) change the secretion of gonadotrophins from ovine adenohypophysis cells in vitro. NO and HDP are produced by pituitary and can modulate gonadotropin secretion by autocrine action. It is possible that these compounds mediate leptin influence on gonadotropin secretion. Therefore, the objective of the present study was to analyse leptin effect on NO and HDP (3-metyl-L-histidine, carnosine and anserine) release from ovine pituitary in vitro. Adenohypophysis cells were cultured in McCoy 5A medium with GnRH (4 x 10(-9) M) and 10(-10)-10(-5) M/l of leptin, respectively. Next, the media for analysis of NO (Griess method) and HDP (HPLC) were collected. Leptin in concentration of 10(-8)-10(-6) M/l caused a significant augmentation in NO in the culture medium, whereas in the dose of 10(-5) M/l reduced (P< or =0.05) NO release. The level of 3-metyl-L-histidine and anserine, but not carnosine, was significantly lower in the culture with 10(-8)-10(-7) M/l of leptin. Taking into account that 10(-8)-10(-7) M/l leptin stimulates LH and FSH secretion, as show in our previous study, it is possible that this effect in ewes is mediated by augmented release of NO and reduction of HDP level.