Leptin inhibits testosterone secretion from adult rat testis in vitro

Leptin, the product of the ob gene, has emerged recently as a pivotal signa l in the regulation of fertility. Although the actions of leptin in the con trol of reproductive function are thought to be exerted mainly at the hypot halamic level, the potential direct effects of leptin at the pituitary and gonadal level have been poorly characterised. In the present study, we firs t assessed the ability of leptin to regulate testicular testosterone secret ion in vitro. Secondly, we aimed to evaluate whether leptin can modulate ba sal gonadotrophin and prolactin (PRL) release by incubated hemi-pituitaries from fasted male rats. To attain the first goal, testicular slices from pr epubertal and adult rats were incubated with increasing concentrations (10( -9)-10(-7) M) of recombinant leptin. Assuming that in vitro testicular resp onsiveness to leptin may be dependent on the background leptin levels, test icular tissue from both food-deprived and normally-fed animals was used. Fu rthermore, leptin modulation of stimulated testosterone secretion was evalu ated by incubation of testicular samples with different doses of leptin in the presence of 10 IU human chorionic gonadotrophin (hCG). In addition, ana lysis of leptin actions on pituitary function was carried out using hemi-pi tuitaries from fasted adult male rats incubated in the presence of increasi ng concentrations (10(-9)-10(-7) M) of recombinant leptin. Serum testostero ne levels, and basal and hCG-stimulated testosterone secretion by incubated testicular tissue were significantly decreased by fasting in prepubertal a nd adult male rats. However, a significant reduction in circulating LH leve ls was only evident in adult fasted rats. Doses of 10(-9)-10(-7) M leptin h ad no effect on basal or hCG-stimulated testosterone secretion by testes fr om prepubertal rats, regardless of the nutritional state of the donor anima l. In contrast, leptin significantly decreased basal and hCG-induced testos terone secretion by testes from fasted and fed adult rats. In addition, 10( -9) M leptin inhibited LH and FSH secretion by incubated hemi-pituitaries f rom fasted adult males, whereas, at all doses tested, it was ineffective in modulating PRL release. Our results show that leptin, depending on the sta te of sexual maturation, is able to inhibit testosterone secretion acting a t the testicular level. Furthermore, the present data suggest that the acti ons of leptin on the reproductive system are complex and are probably carri ed out at different levels of the hypothalamic-pituitary-gonadal axis.