A significant participation of leukemia inhibitory factor in regulating the reproductive function in rats: A novel action of the pleiotropic cytokine

Leukemia inhibitory factor (LIF) is a pleiotropic cytokine exhibiting diver se biological activities in various tissues and cell types. Accumulating ev idence suggests a crucial role for LIF in regulating the hypothalamopituita ry-adrenal axis, but information is limited regarding whether the cytokine also exerts a significant influence on other endocrine systems. In this stu dy, we examined a possible involvement of LIF in the generation of ovarian steroid-induced luteinizing hormone (EH) and prolactin (PRL) surges in the rat. Experiments were performed on both normally fed and 3-day-fasted rats, which were ovariectomized and primed with estradiol and progesterone. From 11:00 to 18:00 h, blood was collected every 30 min to measure LH and PRL. All the following substances were given intracerebroventricularly at 11:00 h, Compared to control serum, undiluted and B-times diluted preparations of anti-rat LIF serum caused a partial but significant suppression of LH surg e to a similar extent, The two different concentrations of antibody also de layed the onset of PRL surge to a comparable degree. Fasted rats were devoi d of significant surges of the hormones, while 1.0 and 3.0 nmol, but not 0. 3 nmol, of recombinant murine LIF given to these animals led to a partial b ut significant recovery of both LH and PRL surges. This stimulatory potency of LIF on both hormones was already maximal at its 1.0-nmol dose. These re sults demonstrate for the first time a significant participation of LIF in the generation of LH and PRL surges in the rat. A novel action of the pleio tropic cytokine is reported herein. (C) 2001 Academic Press.