Effect of acute immunoneutralization of endogenous leptin on prolactin andLH secretion during the afternoon of pro-oestrus or in steroid-treated ovariectomized female rats

Recent data indicate that leptin is involved in the control of reproductive function. Experiments were carried out to analyse the role of endogenous l eptin in the regulation of LH and prolactin secretion during the afternoon of pro-oestrus and that induced by ovarian steroids in ovariectomized rats. In the first experiment, cyclic female rats were implanted with intra-auri cular and intracerebroventricular (i.c.v.) cannulae and, at prooestrus, wer e injected (i.c.v.) with 10 mu l normal rabbit serum or leptin antiserum (a t 13:00 and 14:00 h). Blood samples were obtained at 10:00 h and at interva ls of 1 h between 13:00 and 20:00 h. In the second experiment, female rats in pro-oestrus were injected with normal rabbit serum or leptin antiserum a t 16:00 and 18:00 h and blood samples were taken every 10 min between 18:00 and 20:00 h. In the third experiment, adult female rats that had been ovar iectomized 2 weeks before were implanted with intra-auricular and i.c.v. ca nnulae and treated with oestradiol benzoate (30 mu g s.c.) at 10:00 h and p rogesterone (2 mg s.c.) 48 h later Normal rabbit serum (10 mu l) or leptin antiserum (10 mu l) were injected (i.c.v.) at 13:00 and 14:00 h, and blood samples were obtained at 10:00 h and at intervals of 1 h between 13:00 and 20:00 h. Ln the fourth experiment, hemipituitaries from ovariectomized ster oid-treated female rats were incubated in the presence of leptin(116-130) ( an active fragment of the native molecule), GnRH or leptin + GnRH. Prolacti n and LH secretion during the afternoon of prooestrus in females treated wi th leptin antiserum was similar to that observed in animals injected with n ormal rabbit serum. In ovariectomized female rats, the steroid-induced LH s urge increased slightly after administration of leptin antiserum, whereas t he prolactin surge remained unchanged. In vitro, leptin(116-130) (10(-5) to 10(-8) mol l(-1)) inhibited LH secretion and modulated the effect of GnRH on LH release, depending on the concentration of GnRH: leptin(116-130) (10( -6) mol l(-1)) reduced the effectiveness of 10(-7) mol GnRH l(-1) and incre ased that of 10(-9) mol GnRH l(-1). In conclusion, these experiments indica te that acute immunoneutralization of endogenous leptin does not interfere with spontaneous or steroid-induced LH and prolactin surges. In addition, t he finding that leptin(116-130) inhibited LH release and modulated the effe ctiveness of GnRH in vitro provides evidence of the direct modulatory role of leptin on LH secretion acting at the pituitary.